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In 1972, Diamond et al. [22] for the first time described PDT in an experimental brain tumor model, whereas the first clinical application of this treatment in patients with malignant gliomas was reported in 1980 by Perria et al. [23]. During the next 35 years results of multiple clinical and experimental studies on PDT have been published. Currently it is considered a highly selective local adjuvant treatment option for malignant gliomas; it can be applied either on the residual tumor after it incomplete removal, or on the walls of a resection cavity for elimination of infiltrating neoplastic cells.

To date the largest experience with applications of PDT for gliomas has been gained by the group from Royal Melbourne Hospital, who have applied such treatment to more than 350 patients [5, 16, 24]. The analyzed series of 145 procedures performed between 1986 and 2000 included 59 AA (30 newly diagnosed and 29 recurrent) and 86 GBM (31 newly diagnosed and 55 recurrent). Hematoporphyrin derivative (HpD) in a dose of 5 mg/kg was administered as a photosensitizer 24 h prior to surgery. Maximal tumor resection was followed by direct surface photo-irradiation with a 640 nm laser beam with a range of light energy density from 70 to 240 J/cm². Postoperative fractionated radiotherapy (FRT) was performed in all cases of newly diagnosed tumors, whereas chemotherapy was given in 29% of patients. In newly diagnosed AA and GBM, median survival of patients from the initial diagnosis was 76.5 and 14.3 months, respectively. In recurrent AA and GBM, median survival of patients from the time of repeat surgery was 66.6 and 14.9 months, respectively. The survival rates of patients with newly diagnosed and recurrent GBM were 28 and 40% at 2 years, and 22 and 34% at 5 years, respectively, which was found rather promising compared to historical controls (of note, better outcomes in cases of relapsed neoplasms might be caused by selection bias). Younger age and delivered light energy of ≥230 J/cm² (in cases of newly diagnosed tumors) were defined as favorable prognostic factors [24].

Table 1. Results of photodynamic therapy for glioblastoma

In other clinical series of PDT with the use of various photosensitizers, the median survival time in cases of newly diagnosed GBM has varied from 5 to 31 months, and from 6.7 to 14.9 months in recurrent ones (Table 1) [13, 15, 20, 24–31]. In a small series of 15 patients with newly diagnosed inoperable GBM Stepp [20] presented extraordinary preliminary results of interstitial PDT with 5-ALA, reporting mean progression-free survival (PFS) of 35.5 months and overall survival of 48.8 months. Meta-analysis of observational studies of PDT in high-grade gliomas (HGG) included more than 1,000 patients and reported median survival for newly diagnosed and recurrent GBM of 16.1 and 10.3 months, respectively [6]. Of note, some reports marked a significant number of long-term survivors, with 2-year survival rates of 28–75% for newly diagnosed GBM [24, 25, 30, 31] and 15–40% for recurrent ones [19, 24, 26, 27].