A novel approach to assess the prognostic value of toxicity profiles in gastric cancer patients undergoing preoperative treatment

Background: A substantial proportion of gastric cancer patients develop severe treatment-related toxicity, significantly impacting health-related quality of life. The primary aim of this study was to identify distinct toxicity clusters of gastric cancer patients. The secondary aims were to assess whether cluster membership was associated with event-free (EFS) and overall survival (OS). Methods: Patients who participated in the CRITICS trial (NCT00407186) were included. Toxicity during the first chemotherapy course was examined according to the CTCAE. Agglomerative hierarchical cluster modelling was used to identify patient clusters with distinct toxicity profiles. Cox proportional hazards analysis was performed to assess the association between cluster membership and EFS and OS. Results: 689 of 788 patients (87 %) were included. Four distinct toxicity clusters were identified: a mild toxicity cluster, a neutropenia cluster, a poly toxicity cluster, and a gastrointestinal toxicity cluster. Patients in the neutropenia cluster completed preoperative treatment most often (95 %), completion was lowest in the poly toxicity cluster (76 %; p = 0.003). Patients in the neutropenia toxicity cluster had the longest median OS (58 months) while patients within the gastrointestinal toxicity cluster had the shortest median OS (22 months, p = 0.005). This was also observed for EFS, where the neutropenia toxicity cluster had the longest median EFS of 44 months compared to 13 months in the gastrointestinal toxicity cluster (p = 0.018). Conclusions: In this exploratory study, we identified four distinct toxicity clusters early during preoperative chemotherapy in gastric cancer patients. Cluster membership was prognostic for both EFS and OS, with very large differences between clusters. Patients in the neutropenia toxicity cluster had the best EFS and OS.