Clinical Development of Experimental Therapies for Malignant Glioma

Advances in medical and surgical treatments in the last two to three decades have resulted in quantum leaps in the overall survival of patients with many types of non-central nervous system (CNS) malignant disease, while survival of patients with malignant gliomas (WHO grades 3 and 4) has only moderately improved. Surgical resection, external fractionated radiotherapy and oral chemotherapy, during and after irradiation, remain the pillars of malignant glioma therapy and have shown significant benefits. However, numerous clinical trials with adjuvant agents, most of them administered systemically and causing serious complications and side effects, have not achieved a noteworthy extension of survival, or only with considerable deterioration in patients’ quality of life. Significant attention was focussed in the last decades on the cell biology and molecular genetics of gliomas. Improved understanding of the fundamental features of tumour cells has resulted in the introduction and increasing clinical use of local therapies, which employ spatially defined delivery methods and tumour-selective agents specifically designed to be used in the environment of a glioma-invaded brain. This review summarises the key findings of some of the most recent and important clinical studies of locally administered novel treatments for malignant glioma. Several such therapies have shown considerable anti-tumour activity and a favourable profile of local and systemic side effects. These include biodegradable polymers for interstitial chemotherapy, targeted toxins administered by convection enhanced delivery, and intra- and peritumourally injected genetically modified viruses conferring glioma-selective toxicity. Areas of possible improvement of these therapies and essential future developments are also outlined.

Intraoperative radiotherapy with low-energy x-rays after neurosurgical resection of brain metastases: an Augsburg University Medical Center experience

Purpose!#!External-beam radiotherapy (EBRT) is the predominant method for localized brain radiotherapy (LBRT) after resection of brain metastases (BM). Intraoperative radiotherapy (IORT) with 50-kV x‑rays is an alternative way to focally irradiate the resection cavity after BM surgery, with the option of shortening the overall treatment time and limiting normal tissue irradiation.!##!Methods!#!We retrospectively analyzed the outcomes of all patients who underwent neurosurgical resection of BM and 50-kV x‑ray IORT between 2013 and 2020 at Augsburg University Medical Center.!##!Results!#!We identified 40 patients with 44 resected BM treated with 50-kV x‑ray IORT. Median diameter of the resected metastases was 2.8 cm (range 1.5-5.9 cm). Median applied dose was 20 Gy. All patients received standardized follow-up (FU) including 3‑monthly MRI of the brain. Mean FU was 14.4 months, with a median MRI FU for alive patients of 12.2 months. Median overall survival (OS) of all treated patients was 26.4 months (estimated 1‑year OS 61.6%). The observed local control (LC) rate of the resection cavity was 88.6% (estimated 1‑year LC 84.3%). Distant brain control (DC) was 47.5% (estimated 1‑year DC 33.5%). Only 25% of all patients needed WBI in the further course of disease. The observed radionecrosis rate was 2.5%.!##!Conclusion!#!IORT with 50-kV x‑rays is a safe and appealing way to apply LBRT after neurosurgical resection of BM, with low toxicity and excellent LC. Close MRI FU is paramount to detect distant brain failure (DBF) early