Prognostic Factors and Talaporfin Sodium Concentration in Photodynamic Therapy for Recurrent Grade 4 Glioma

<b>Background:</b> Although extensive resection improves the prognosis of gliomas, it risks impairing critical brain functions. Photodynamic therapy (PDT) utilizing talaporfin sodium (TS) targets tumor cells upon light activation. Despite its approval in Japan, TS application remains restricted, and factors influencing its efficacy are unclear. We aimed to identify TS efficacy determinants to optimize treatment outcomes. <b>Methods:</b> Data from 171 patients with grade 4 glioma who underwent surgery and PDT at Tokyo Women's Medical University Hospital between January 2017 and March 2024 were retrospectively analyzed. Clinical variables evaluated included age, sex, genotype, Karnofsky Performance Status (KPS), serum albumin (Alb) levels, MIB-1 expression levels, and medication history. TS concentrations in tumor tissues were quantitatively assessed in 82 patients (41 primary, 41 recurrent). Survival outcomes were analyzed. RNA-seq was performed on the three highest and three lowest TS concentration samples with significant TS concentration variations to investigate corresponding gene expression changes. <b>Results:</b> Multivariate analysis identified KPS (hazard ratio [95% confidence interval]: 0.96 [0.93-0.99], <i>p</i> = 0.01) and Alb (3.68 [1.05-13.76], <i>p</i> = 0.047) as independent prognostic factors. In recurrent cases, higher TS concentrations were significantly associated with improved survival (<i>p</i> = 0.0454). RNA-seq analysis indicated decreased expression of <i>ACTB</i> and <i>PDPN</i> genes in samples with lower TS concentrations, suggesting potential resistance mechanisms. <b>Conclusions:</b> TS concentration is a critical determinant of PDT efficacy, especially in recurrent glioma, highlighting its prognostic significance. Alb may affect treatment outcomes by mediating TS binding. RNA-seq findings imply that low TS concentrations may suppress immune and stress response-related genes, potentially diminishing PDT sensitivity.