The oral medicine–oncology nexus: Periodontal disease as a predictor of survival and complications in immunotherapy-treated melanoma.

Abstract

e21599 Background: Immune checkpoint inhibitors have transformed melanoma treatment, but comorbidities like periodontal disease—pre-existing or immune-related adverse events—may modulate efficacy and toxicity through systemic inflammation and immune dysregulation. This study examined associations between periodontal disease (any-time diagnosis) and clinical outcomes, including mortality and systemic complications, in melanoma patients receiving immunotherapy. Methods: This retrospective cohort study used the TriNetX federated network of deidentified electronic medical records from 88 healthcare organizations. Adults (aged ≥18 years) with melanoma (ICD-10-CM C43-C44) receiving immunotherapy (pembrolizumab or antineoplastic immunotherapy encounter) were stratified by presence (n = 703) or absence (n = 37,419) of periodontal disease (ICD-10-CM K05). Propensity score matching (1:1) balanced race, communicable disease hazards, body mass index, and Eastern Cooperative Oncology Group performance status, yielding 698 patients per group. Analysis was performed January 24, 2026. The primary outcome was all-cause mortality, with secondary outcomes of circulatory (I00-I99), endocrine/metabolic (E00-E89), respiratory (J00-J99), and digestive (K00-K95) diseases; fever of unknown origin (R50); and symptoms involving food/fluid intake (R63), circulatory/respiratory systems (R00-R09), and digestive system/abdomen (R10-R19). Outcomes were assessed from 1 day post-index event (melanoma diagnosis) onward. Analyses included risk differences, ratios, odds ratios, Kaplan-Meier survival (log-rank), Cox hazard ratios, and instance counts excluding prior events. Results: Post-matching, mortality was higher in the periodontal group (41.7% vs 34.8%; risk difference −0.069 [95% CI, −0.120 to −0.018]; P = .008; risk ratio 0.835 [95% CI, 0.730-0.955]; odds ratio 0.746 [95% CI, 0.601-0.927]) with shorter median survival (1271 vs 1626 days; log-rank P = .002; hazard ratio 0.763 [95% CI, 0.643-0.906]; P = .016). Significant associations included fever of unknown origin (hazard ratio 0.682 [95% CI, 0.495-0.939]; log-rank P = .018) and food/fluid intake symptoms (22.3% vs 14.8%; risk difference −0.075 [95% CI, −0.125 to −0.024]; P = .003; hazard ratio 0.603 [95% CI, 0.445-0.817]). No significant differences emerged for circulatory (P = .288), endocrine/metabolic (P = .268), respiratory (P = .999), or digestive symptoms (P = .756 for digestive symptoms; disease analysis precluded due to 0 events in periodontal group). Conclusions: Periodontal disease is linked to poorer survival and select complications in immunotherapy-treated melanoma patients. These findings advocate for routine periodontal evaluation and intervention to potentially enhance oncologic outcomes.