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Our extensive basic research on photodynamic therapy (PDT) application in models of intracranial malignant astrocytoma led to its clinical application for intracranial malignant astrocytoma in Japan. Having considered the safety and effectiveness of this pathology, we initiate a first-in-human clinical study of PDT for spinal cord malignant astrocytoma. This study has an open-label, single-arm design. The initial follow-up period is 12 months, at the end of which we will quantify survival after PDT for spinal cord malignant astrocytoma as primary objective. The secondary objective is to quantify the overall progression-free survival of treated patients and the percentage of patients surviving 6 months after PDT without recurrence. Twenty patients suffering from spinal cord malignant astrocytoma will be recruited. In particular, 10 of those should be newly diagnosed World Health Organization grade 4. After obtaining consent, each patient will receive a single intravenous injection of talaporfin sodium (40 mg/m2) 1 day before tumor resection. One day after completing tumor removal, the residual lesion and/or resection cavity will be irradiated using a 664-nm semiconductor laser with a radiation power density of 150 mW/cm2 and a radiation energy density of 27 J/cm2. The procedure will be performed 22–26 hours after talaporfin sodium administration. This study protocol has been reviewed and approved by the Certified Committee in the Japanese Ministry of Health, Labor, and Welfare University Hospital Medical Information Network Clinical Trials Registry (Japan Registry of Clinical Trials number, jRCT2021220040). [ABSTRACT FROM AUTHOR]

This preclinical study was conducted to investigate the efficacy of interstitial PDT (i-PDT) for malignant gliomas arising deep within the brain, which are difficult to remove. C6 glioma cells were implanted into the basal ganglia of rats, and 3 weeks later, the second-generation photosensitizer talaporfin sodium (TPS) was administered intraperitoneally. Ninety minutes after administration, a prototype fine plastic optical fiber was punctured into the tumor tissue, and semiconductor laser light was irradiated into the tumor from a 2-mm cylindrical light-emitting source under various conditions. The brain was removed 24 h after the i-PDT and analyzed pathologically. The optical fiber was able to puncture the tumor center in all cases, enabling i-PDT to be performed. Histological analysis showed that tumor necrosis was induced in areas close to the light source, correlating with the irradiation energy dose, whereas apoptosis was induced at some distance from the light source. Irradiation using high energy levels resulted in tissue swelling from strong tumor necrosis, and irradiation at 75 J/cm2 was most suitable for inducing apoptosis. An experimental system of i-PDT using TPS was established using malignant glioma cells transplanted into the rat brain. Tumor cell death, which correlated with the light propagation, was induced in tumor tissue. [ABSTRACT FROM AUTHOR]

A 72‐year‐old woman with dermatomyositis (DM) developed neurological manifestation, and magnetic resonance imaging (MRI) revealed multiple T2/fluid‐attenuated inversion recovery (FLAIR)‐hyperintense lesions predominantly in the deep white matter of the cerebral hemisphere. Punctate or linear contrast enhancement was observed surrounding the T1‐hypointense area. Multiple T2/FLAIR‐hyperintense lesions were aligned along with the corona radiata. Malignant lymphoma was first suspected, and a brain biopsy was performed. Pathological investigation suggested the provisional diagnosis of "suspicious of malignant lymphoma." Owing to emergent clinical conditions, high‐dose methotrexate (MTX) therapy was conducted, and then T2/FLAIR‐hyperintense lesions were dramatically reduced. However, the diagnosis of malignant lymphoma was concerning since multiplex PCR demonstrated clonal restriction of the Ig H gene for B cells and TCR beta genes for T cells. Histopathology revealed the infiltration of both CD4+ and CD8+ T cells, and the CD4+/CD8+ ratio was 4.0. Moreover, prominent plasma cells were observed, in addition to CD20+ B cells. Atypical cells with enlarged nuclei were present, and they were not hematopoietic but found as glial cells. JC virus (JCV) infection was verified with both immunohistochemistry and in situ hybridization; the final diagnosis was progressive multifocal leukoencephalopathy (PML). The patient was treated with mefloquine and discharged. This case is informative in understanding the host anti‐viral response. Variable inflammatory cells were observed, including CD4+ and CD8+ T cells, plasma cells, and a small amount of perivascular CD20+ B cells. PD‐1 and PD‐L1 expression was observed in lymphoid cells and macrophages, respectively. PML with inflammatory reactions was thought fatal, and autopsy cases of PML with immune reconstitution inflammatory syndrome (IRIS) demonstrated excessive infiltration of only CD8+ T cells. However, this case revealed infiltration of variable inflammatory cells, and a favorable prognosis would be expected under PD‐1/PD‐L1 immune‐checkpoint regulation. [ABSTRACT FROM AUTHOR]

The aim of this study was to demonstrate the clinical feasibility of intraoperative additional photodynamic therapy (PDT) using talaporfin sodium and a semiconductor laser in patients with malignant meningeal tumors. 14 patients (Male / Female: 5 / 9, aged 41 to 80 y.o.) were enrolled in this study. Except for 1 case, almost all cases are recurrent meningeal tumor usually demonstrated the long clinical history, median 60 (11 to 420) months, including multiple surgery and radiotherapy. The locations of these tumors were parasagittal/ convexity 7, middle fossa/petrous 3, cerebellopontine angle 3 and tentorium cerebelli 1. Except for 3 cases of hemangiopericytoma/solitary fibrous tumor Grade III, 10 cases were consisted of 4 atypical and 6 anaplastic meningioma. The method of PDT was identical to the reported one for malignant glioma cases. (Akimoto J, Neurol Med Chir 2016). 4 cases were performed repeat resection with PDT for repeated recurrence. The resection rate of 19 times of surgery were total resection 1, Simpson Grade II 7 and Grade IV 11 cases, respectively. The median follow up period from first PDT was 23.5 (6 to 45) months. The average number of laser irradiation to the attached dura mater or invading brain tissue was 8.8 (2 to 29). Except for 1 case of 6 months survival time with 15 years clinical history and 3 cases of 2 to 3 years survival time, other 10 cases were still alive. No adverse events directly attributable to PDT occurred in any patients. Protection against light was only required for approximately 7 days after PDT. There are few therapeutic strategies of recurrent atypical/anaplastic meningeal tumor. It is an urgent issue to develop the effective local treatment to manage these complicated tumors. The results of the present study suggest that PDT with talaporfin sodium provides excellent local control without adverse event for patients with malignant meningeal tumors. [ABSTRACT FROM AUTHOR]