Photodynamic therapy for malignant brain tumors in children and young adolescents

Abstract

Photodynamic therapy (PDT) targets tumor cell remnants after resection. Here, we evaluated the feasibility of PDT for malignant brain tumors in children and young adolescents. This was a single-center, non-randomized, phase I/II clinical study. The primary endpoints were the safety of treatment with talaporfin sodium (TS) (phase I) and overall survival (OS) after PDT (phase II). The secondary endpoint was progression-free survival (PFS) after PDT. The TS dose was determined by dose escalation from 10 to 20 to 40 mg/m2 for every three cases starting from the initial enrolled case. Eight patients with a mean age of 170.2 months (129–214 months) at the time of PDT received nine procedures with a mean follow-up duration of 16.8 months (1–42 months) after PDT. Histopathological diagnoses included supratentorial anaplastic ependymoma (n = 2), anaplastic astrocytoma (n = 1), diffuse midline glioma with H3K27M mutation (n = 1), glioblastoma (n = 3), and pediatric high-grade glioma (n = 1). The outcome was survival in five patients and death in three patients. Recurrence occurred in six of the eight patients; the remaining two were recurrence-free after PDT. Therefore, OS and PFS were calculated as 21 and 6 months, respectively. Seizures and fevers, which were likely surgery-related symptoms, were commonly observed. Photosensitive skin rashes or liver dysfunction, which are common adverse effects in adults, were not observed. Our results showed that TS can be used safely in children at doses comparable to those used in adults, as there was no major complication associated with TS administration. However, we cannot make a definitive conclusion about the efficacy of PDT because of the small number of participants. Accumulating cases was difficult because of the rarity of pediatric brain tumors and the difficulty in making a preoperative differential diagnosis, considering the wide range of histopathological findings. Moreover, the psychological stress associated with light-shielding management in pediatric patients was more severe than initially expected. In conclusion, TS at doses comparable to those used in adults may be safe for use in children and young adolescents between the ages of 6 and 20 years. However, further studies are needed to clarify its efficacy.

Systematic Review of Photodynamic Therapy in Gliomas

“…One of the most recent reports evaluating PDT feasibility for malignant pediatric brain tumors has reported on treatment using TS in children and young adolescents with brain tumors, including diffuse midline glioma (DMG), glioblastoma, and high-grade glioma. Not only was TS PDT found to be safe for use at dosages comparable to those used in adults, but adverse events commonly identified in adult patients were also not found in children following therapy [220]. These results are incredibly encouraging for PDT usage for pediatric CNS tumors.…”

Pharmaceutical Approach to Develop Novel Photosensitizer Nanoformulation: An Example of Design and Characterization Rationale of Chlorophyll α Derivative

“…Photodynamic therapy (PDT) has emerged as a highly sought-after oncology treatment, with earliest applications dating back to the early 1900s [ 1 ]. PDT effectively targets superficial neoplasms and microscopic residual tumors after resection, making it a valuable therapeutic modality [ 2 , 3 ]. This treatment modality involves the local activation of a photosensitizer (PS) by visible red light, triggering the production of reactive oxygen species that selectively kill cancer cells.…”

Photobac derived from bacteriochlorophyll-a shows potential for treating brain tumor in animal models by photodynamic therapy with desired pharmacokinetics and limited toxicity in rats and dogs

“…There is no established therapy in recurrent glioblastoma that is associated with any survival benefit and there is an urgent need for better therapeutic options. Since local control remains inadequate, there is a strong rational for the development of adjuvant treatments to enhance the destruction of tumor cells located beyond the margin of surgical resection [ 11 , 12 ] and Photodynamic therapy offers one such option [ 13 – 15 ].…”