Abstract
BackgroundGlioblastoma multiforme (GBM), the most common malignant brain tumor, mainly manifests as a primary de novo and less frequently as a secondary glial neoplasm. GBM has been demonstrated to overexpress the NK-1 receptor and substance P can be used as a ligand for targeted therapy. Alpha emitters, e.g. 213Bi, that deposit their high energy within a short range allow the selective irradiation of tumor cells while sparing adjacent neuronal structures.Material and methodsAmong 50 glioma patients of different subtypes that have to date been treated with targeted alpha therapy at the Medical University Warsaw, we report here the data on nine patients with secondary GBM. Following surgery, chemo- and radiotherapy, recurrent GBM was treated by intracavitary injection of 1–6 doses of 0.9–2.3 GBq 213Bi- DOTA-[Thi8,Met(O2)11]-substance P (213Bi-DOTA-SP) in 2-month intervals. 68Ga-DOTA-[Thi8,Met(O2)11]-substance P (68Ga-DOTA-SP) was co-injected with the therapeutic doses to assess biodistribution using PET/CT. Therapeutic response was monitored with MRI.ResultsTreatment with activities ranging from 1.4 to 9.7 (median 5.8) GBq 213Bi- DOTA-SP was well tolerated with only mild transient adverse reactions, mainly headaches due to a transient perfocal edema reaction. The median progression free survival and overall survival time following the initiation of alpha therapy was 5.8 and 16.4 months, respectively. The median overall survival time from the first diagnosis was 52.3 months. Two out of nine patients are still alive 39 and 51 months, respectively, after the initiation of the therapy.ConclusionsTargeted alpha therapy of secondary GBM with 213Bi-DOTA-SP is safe and well tolerated and may evolve as a promising novel therapeutic option for secondary GBM.
Highlights
Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor which evolves either as a primary de novo GBM or as a transformed secondary GBM out of a less malignant precursor lesion
This paper presents the results of targeted alpha therapy (TAT) with radio-labelled 213Bi-DOTA-Substance P analogue in nine patients with secondary GBM
Clinical and histopathological criteria were used to distinguish between glioblastoma subtypes: primary GBM was histopathologically defined as grade IV lesion at the first biopsy, without clinical or histopathologic evidence of a less malignant precursor lesion
Summary
Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor which evolves either as a primary de novo GBM or as a transformed secondary GBM out of a less malignant precursor lesion. The addition of temozolamide chemotherapy to standard external beam radiotherapy led to a mean survival of 14.6 months, as compared to 12.1 months with radiotherapy alone [3]. This more aggressive combination of therapies has some limitations, e.g. severe fatigue, thromboembolic events or opportunistic infections of mainly lung tissue [7,8,9]. Glioblastoma multiforme (GBM), the most common malignant brain tumor, mainly manifests as a primary de novo and less frequently as a secondary glial neoplasm. Chemo- and radiotherapy, recurrent GBM was treated by intracavitary injection of 1–6 doses of 0.9–2.3 GBq 213Bi- DOTA-[Thi8,Met(O2)11]substance P (213Bi-DOTA-SP) in 2-month intervals.
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