Development and internal validation of a clinical risk score to predict incident renal and pulmonary tumours in people with tuberous sclerosis complex.

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.
Competing Interests: 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.
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