Immunosuppression and post-transplant lifetime cancer risk among solid organ transplant recipients in Quebec
Bibliographic record
Abstract
Introduction: Solid Organ Transplantation (SOT) is a treatment of choice for individuals who face end-stage organ failure. Annually, over 2800 Canadians and 500 Quebecers undergo solid organ transplantation. This group experiences 2-4 times higher lifetime cancer risk, post-transplantation, compared to the general population. This heightened risk has been attributed to the use of immunosuppressive agents (IA’s). With the anticipated increase in cancer incidence in Quebec in the coming decade, there is a significant gap in understanding the impact of IAs on cancer risk among SOT recipients in the province. Objective 1: 1. a) To estimate the post-transplant lifetime cancer incidence rate among SOT recipients in Quebec, from 1997-2016; 1. b) To compare the cancer burden, calculated the age and sex standardized incidence, between SOT recipients and the general population of Quebec from 1997 to 2016.2: To estimate the average treatment effect of modern-era IA, compared to early-era IA, on the post-transplant lifetime risk of developing any cancer among SOT recipients. Methods: We constructed a retrospective cohort study by linking two provincial-level administrative healthcare databases from 1997 to 2016: i) the Régie de l’assurance maladie du Québec (RAMQ), and ii) Maintenance et exploitation des données pour l’étude de la clientèle hospitalière (Med-ECHO). We analyzed the pattern of cancer incidence by organ transplanted and computed the overall incidence rate stratified by sex. Age and sex standardized incidence per 100,000 for the general population of Quebec obtained from the Quebec Cancer Registry. Subsequently, the direct standardization method was used to estimate the standardized risk ratio between our cohort and Quebec general population, while using the 2011 Quebec population as the standard reference population. To estimate the causal effect of being prescribed one of the modern-era IAs (Mycophenolate mofetil, Sirolimus, and Tacrolimus), compared to one of the early-era drugs (Azathioprine and Cyclosporine), we followed the potential outcomes framework for causal inference. Following this framework, to emulate a target trial from observational data we used Bayesian Additive Regression Trees (BART) models for both treatment assignment mechanism and outcome model. We further corrected the estimate of interest (population average treatment effect) following the recommended Targeted Minimum loss-based estimation method. The average reduction in cancer risk (in risk difference scale) attributable to prescribing one of the modern era IA to all SOT recipients in Quebec who were prescribed one of the early era IA and the corresponding 95% credible intervals were estimated. Results: We identified 6,783 SOT recipients and based on ICD codes, we identified 1,142 post-transplant cancer cases, with an overall incidence rate of 2,436.1 per 100,000 person-years (95%CI; 2,212 -2,486 per 100,000 person-years). Skin cancer was the common cancer among SOT recipients. The age and sex standardized risk ratio indicated a 2.5-to-4.2-fold increase in cancer risk among SOT recipients compared to the general population of Quebec between 1997-2016. In our analytical cohort, 4,892 individuals were prescribed a baseline maintenance therapy regimen, with a median of 6.93 years of follow-up. During this period, 909 individuals developed at least one primary malignant neoplasm. The SOT recipients who were originally prescribed one of the early-era IAs would have had 4% points lower post-transplant cancer risk if they had been prescribed one of the modern-era IAs, instead (RD= -0.040; 95%CI = -0.049 to -0.030). Conclusion: SOT recipients in the province of Quebec were at a significantly higher risk for cancer compared to the general population. Switching to modern-era immunosuppressive agents (e.g., Mycophenolate mofetil, Sirolimus, and Tacrolimus), from early-era IAs, may reduce the lifetime risk of any cancers among SOT recipients in Quebec
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".