Therapeutic Options for Recurrent Glioblastoma-Efficacy of Talaporfin Sodium Mediated Photodynamic Therapy

Abstract

Recurrent glioblastoma (GBM) remains one of the most challenging clinical issues, with no standard treatment and effective treatment options. To evaluate the efficacy of talaporfin sodium (TS) mediated photodynamic therapy (PDT) as a new treatment for this condition, we retrospectively analyzed 70 patients who underwent surgery with PDT (PDT group) for recurrent GBM and 38 patients who underwent surgery alone (control group). The median progression-free survival (PFS) in the PDT and control groups after second surgery was 5.7 and 2.2 months, respectively (p = 0.0043). The median overall survival (OS) after the second surgery was 16.0 and 12.8 months, respectively (p = 0.031). Both univariate and multivariate analyses indicated that surgery with PDT and a preoperative Karnofsky Performance Scale were significant independent prognostic factors for PFS and OS. In the PDT group, there was no significant difference regarding PFS and OS between patients whose previous pathology before recurrence was already GBM and those who had malignant transformation to GBM from lower grade glioma. There was also no significant difference in TS accumulation in the tumor between these two groups. According to these results, additional PDT treatment for recurrent GBM could have potential survival benefits and its efficacy is independent of the pre-recurrence pathology.

Keywords: lower grade glioma; photodynamic therapy; photosensitizer; recurrent glioblastoma; talaporfin sodium.

Figure 1

Kaplan–Meier survival curves for PFS and OS after surgery for recurrence in the PDT and control groups. (A) Patients in the PDT group showed significantly longer PFS than the patients in the control group (median PFS: PDT 5.7 months, control 2.2 months; p = 0.0043). (B) Patients in the PDT group showed significantly longer OS than the patients in the control group (median OS: PDT 16.0 months, Control 12.8 months; p = 0.031).

Figure 2

Kaplan–Meier survival curves for PFS and OS after surgery for recurrence in the GBM and LGG groups. (A) The PFS was not significantly different between the GBM and LGG groups (median PFS: GBM 6.3 months, LGG 4.2 months; p = 0.31). (B) The OS was not significantly different between the GBM and LGG groups (median OS: GBM 15.4 months, LGG 18.3 months; p = 0.91).

Figure 3

HE staining and fluorescence microscopy images of normal brain tissue surrounding the tumor (A,B) and recurrent glioblastoma in contrast-enhanced lesions (C,D). Samples were processed for H&E staining or immunofluorescence examination. The nuclei of the tumor cells were stained with DAPI, and red fluorescence at 640 nm was detected in the tumor cells at an excitation wavelength of 400 nm, which indicated the TS uptake in the tumor and normal brain tissue. Abbreviations: CE, contrast enhanced.

Figure 4

Fluorescence intensity in CE region of recurrent glioblastoma samples from GBM (n = 14) and LGG (n = 6) groups. There was no significant difference between the two groups (Mann–Whitney U test, p = 0.20). Each box represents the interquartile range, and the median was indicated by a bold line. The ends of the whiskers represented the 10th and 90th percentile.

Figure 5

Representative Case 1. Contrast-enhanced T1-weighted and FLAIR MR image before (A,B) and after (C,D) the first operation. Contrast-enhanced T1-weighted and FLAIR findings before the second operation with PDT (E,F); 3 days (G,H); 2 weeks (I,J); 2 months (K,L), and 47 months (M,N) after the second surgery.

Figure 6

Representative Case 2. Contrast-enhanced T1-weighted and FLAIR MR image before (A,B) and after (C,D) the first operation. Contrast-enhanced T1-weighted and FLAIR findings before the second operation with PDT (E,F); 3 days (G,H); 2 weeks (I,J); 2 months (K,L); 5 months (M), and 50 months (O,P) after the second surgery. PET study at 5 months postoperatively (N). The pathological results of the suspected recurrent lesion at 5 months postoperatively showed venous infarction ((Q) arrowhead) and loss of internal elastic membrane ((Q) arrow), but no obvious tumor cells (R).