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Original research
Development and internal validation of a clinical risk score to predict incident renal and pulmonary tumours in people with tuberous sclerosis complex
  1. Frédéric Loubert1,
  2. Andrew A House2,
  3. Catherine Larochelle3,4,
  4. Philippe Major5,
  5. Mark R Keezer1,4
  1. 1CRCHUM, Montreal, Quebec, Canada
  2. 2London Health Sciences Centre, London, Ontario, Canada
  3. 3Université de Montréal, Montreal, Quebec, Canada
  4. 4Department of Neurosciences, Université de Montréal, Montreal, Quebec, Canada
  5. 5Research Center, Saint Justine University Hospital Research Centre, Montreal, Quebec, Canada
  1. Correspondence to Dr Mark R Keezer, CRCHUM, Montreal, QC H2X 0C1, Canada; mark.keezer{at}umontreal.ca

Abstract

Objective This study aims to develop and internally validate a clinical risk score to predict incident renal angiomyolipoma (AML) and pulmonary lymphangioleiomyomatosis (LAM) in people with tuberous sclerosis complex (TSC).

Study design Data from 2420 participants in the TSC Alliance Natural History Database were leveraged for these analyses. Logistic regression was used to predict AML and LAM development using 10 early-onset clinical manifestations of TSC as potential predictors, in addition to sex and genetic mutation. For our models, we divided AML into three separate outcomes: presence or absence of AML, unilateral or bilateral and whether any are ≥3 cm in diameter. The resulting regression models were turned into clinical risk scores which were then internally validated using bootstrap resampling, measuring discrimination and calibration.

Results The lowest clinical risk scores predicted a risk of AML and LAM of 1% and 0%, while the highest scores predicted a risk of 99% and 73%, respectively. Calibration was excellent for all three AML outcomes and good for LAM. Discrimination ranged from good to strong. C-statistics of 0.84, 0.83, 0.83 and 0.92 were seen for AML, bilateral AML, AML with a lesion≥3 cm and LAM, respectively.

Conclusion Our work is an important step towards identifying individuals who could benefit from preventative strategies as well as more versus less frequent screening imaging. We expect that our work will allow for more personalised medicine in people with TSC. External validation of the risk scores will be important to confirm the robustness of our findings.

  • Prognosis

Data availability statement

Data may be obtained from a third party and are not publicly available. Data may be obtained from the TSC Alliance through the research data request form (https://www.tscalliance.org/researchers/natural-history-database/).

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Data availability statement

Data may be obtained from a third party and are not publicly available. Data may be obtained from the TSC Alliance through the research data request form (https://www.tscalliance.org/researchers/natural-history-database/).

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Footnotes

  • Presented at This research builds upon work originally presented in the author’s thesis, titled ‘Développement et validation interne de scores de risque clinique afin de prédire le risque de tumeurs rénales et pulmonaires chez les gens atteints de la sclérose tubéreuse de Bourneville’ (‘Development and internal validation of clinical risk scores to predict the risk of renal and pulmonary tumors in people with tuberous sclerosis complex’), submitted to School of Public Health of the Université de Montréal in 2023.

  • Contributors FL: Data collection, study design, data collection, data analyses, writing of first draft, review and editing of manuscript. MRK: Guarantor, conceptualisation of the research project, supervision of the research project, study design, data collection, revision and editing of data analyses, revision and editing of manuscript. AAH: Study design, revision and editing of manuscript. CL: Study design, revision and editing of manuscript. PM: Study design, revision and editing of manuscript.

  • Funding This study was supported by the TD Bank Ready Commitment programme.

  • Disclaimer The views expressed in this article are those of the authors and do not necessarily reflect the opinion of the TSC Alliance.

  • Competing interests MRK: Unrestricted educational grants from UCB, Eisai and Jazz Pharmaceuticals, as well as research grants for investigator-initiated studies from UCB and Eisai. PM: Local principal investigator for projects 1501, 1503, 1504, studying fenfluramine in patients with Dravet syndrome, funded by Zogenix. Local principal investigator for project 1042-TSC-3002, A phase 3, open-label study of adjunctive ganaxolone treatment in children and adults with TSC-related epilepsy, funded by Marinus Pharmaceuticals Invited speaker, UCB. Consultant, Jazz Pharma.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.