An Unsupervised Machine Learning Approach to Evaluating the Association of Symptom Clusters With Adverse Outcomes Among Older Adults With Advanced Cancer: A Secondary Analysis of a Randomized Clinical Trial
Menée à partir des données portant sur 706 patients âgés atteints d'un cancer de stade avancé et inclus dans un essai randomisé (âge moyen : 77,2 ans), cette étude analyse l'intérêt d'une approche par apprentissage automatique non supervisé pour évaluer la sévérité de leurs symptômes et prédire le risque d'hospitalisations associées ainsi que la mortalité à 1 an
Importance : Older adults with advanced cancer who have high pretreatment symptom severity often experience adverse events during cancer treatments. Unsupervised machine learning may help stratify patients into different risk groups.
Objective : To evaluate whether clusters identified from baseline patient-reported symptom severity were associated with adverse outcomes.
Design, Setting, and Participants : This secondary analysis of the Geriatric Assessment Intervention for Reducing Toxicity in Older Patients With Advanced Cancer (GAP70+) Trial (2014-2019) included patients who completed the National Cancer Institute Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) before starting a new cancer treatment regimen and received care at community oncology sites across the United States. An unsupervised machine learning algorithm (k-means with Euclidean distance) clustered patients based on similarities of baseline symptom severities. Clustering variables included severity items of 24 PRO-CTCAE symptoms (range, 0-4; corresponding to none, mild, moderate, severe, and very severe). Total severity score was calculated as the sum of 24 items (range, 0-96). Whether the clusters were associated with unplanned hospitalization, death, and toxic effects was then examined. Analyses were conducted in January and February 2022.
Exposures : Symptom severity.
Main Outcomes and Measures : Unplanned hospitalization over 3 months (primary), all-cause mortality over 1 year, and any clinician-rated grade 3 to 5 toxic effect over 3 months.
Results : Of 718 enrolled patients, 706 completed baseline PRO-CTCAE and were included (mean [SD] age, 77.2 [5.5] years, 401 [56.8%] male patients; 51 [7.2%] Black and 619 [87.8%] non-Hispanic White patients; 245 [34.7%] with gastrointestinal cancer; 175 [24.8%] with lung cancer; mean [SD] impaired Geriatric Assessment domains, 4.5 [1.6]). The algorithm classified 310 (43.9%), 295 (41.8%), and 101 (14.3%) into low-, medium-, and high-severity clusters (within-cluster mean [SD] severity scores: low, 6.3 [3.4]; moderate, 16.6 [4.3]; high, 29.8 [7.8]; P < .001). Controlling for sociodemographic variables, clinical factors, study group, and practice site, compared with patients in the low-severity cluster, those in the moderate-severity cluster were more likely to experience hospitalization (risk ratio, 1.36; 95% CI, 1.01-1.84; P = .046). Moderate- and high-severity clusters were associated with a higher risk of death (moderate: hazard ratio, 1.31; 95% CI, 1.01-1.69; P = .04; high: hazard ratio, 2.00; 95% CI, 1.43-2.78; P < .001), but not toxic effects.
Conclusions and Relevance : In this study, unsupervised machine learning partitioned patients into distinct symptom severity clusters; patients with higher pretreatment severity were more likely to experience hospitalization and death.
Trial Registration ClinicalTrials.gov Identifier: NCT02054741
JAMA Network Open , résumé, 2022