Assessing Clinical Disease Recurrence Using Laboratory Data in Surgically Resected Patients From the TOPPIC Trial

Background Machine learning methodologies play an important role in predicting progression of disease or responses to medical therapy. We previously derived and validated a machine learning algorithm to predict response to thiopurines in an inflammatory bowel disease population. We aimed to apply a modified algorithm to predict postsurgical treatment response using clinical trial data. Methods TOPPIC was a multicenter randomized double-blinded placebo-controlled trial of 240 patients, evaluating the effectiveness of 6-mercaptopurine in preventing or delaying postsurgical Crohn disease recurrence. We adapted a well-established machine learning algorithm to predict clinical recurrence postresection using age and multiple laboratory-specific covariates, and compared this to the thiopurine metabolite, 6-thioguanine. Results The random forest machine learning algorithm demonstrates a mean under the receiver operator curve (AuROC) of 0.62 [95% confidence interval (CI) 0.47, 0.78]. Similar results were evident when adding thiopurine metabolite (6-thioguanine) results. Alanine aminotransferase/mean corpuscular volume (ALT/MCV) and potassium × alkaline phosphatase (POT × ALK) predicted endoscopic and biologic recurrence, respectively, with AuROCs of 0.714 (95% CI 0.601, 0.827) and 0.730 (95% CI 0.618, 0.841). Conclusions A machine learning algorithm with laboratory data from within the first 3 months postsurgically does not discriminate clinical recurrence well. Alternative noninvasive measures should be considered and further evaluated.