Recently, 5-aminolevulinic acid (5-ALA) has been utilized as an adjuvant to the surgical resection of primary brain tumors and metastases. We conducted a systematic review of the literature to further understand the role of 5-ALA in neurosurgery. Our goal was to identify the utility of 5-ALA during resection by evaluating its sensitivity and specificity for different tumor types, as well as the extent of tumor resection achieved while using 5-ALA. A search of the literature was conducted using the PubMed database for the period January 1990 through May 2014. Surgical series in which 5-ALA was used for brain neoplasm resections were evaluated for tumor histology, sensitivity, specificity, extent of resection, complications, and outcomes. Twenty-two series, involving 1163 patients, were included in our review. 5-ALA sensitivity was highest in high-grade gliomas (85 %) and meningiomas (81 %). 5-ALA specificity was high in meningiomas (100 %), as well as metastases (84 %) and high-grade gliomas (82 %). Gross total resection (GTR) was achieved using 5-ALA in 66.2 % of all gliomas and 69.6 % of meningiomas, regardless of histological subtype. 5-ALA may be a useful tool in increasing the extent of resection and achieving GTR in intracranial tumors. The resection of tumors for which 5-ALA has high sensitivity and specificity, such as high-grade gliomas, may lead to an increase in extent of resection when compared to operations using only standard white light. Further evidence for the use of 5-ALA in meningiomas and certain subtypes of metastases may be needed to qualify its efficacy.

Brachytherapy (BT) for glioblastoma multiforme (GBM) involves the use of radioactive isotopes to deliver ionizing radiation directly into the tumor bed. Its application as a means to prolong survival in GBM patients over the past few decades has come with variable success. The objective of this review is to describe the utility of BT in GBM, and to report the outcomes and adverse events associated with its use in different multimodal treatment approaches. A search of the literature was conducted using the PubMed database. The most recent search was performed in September 2015. Thirty-two series involving 1571 patients were included in our review. The longest median overall survival (MOS) following BT for newly diagnosed GBM reached 28.5 months. Overall, 1-, 2-, and 3-year survival rates were 46-89 %, 20-57 %, and 14-27 %. For recurrent GBM, the longest reported MOS after BT was 15.9 months. One-, 2- and 3-year survival rates for recurrent GBM were 10-66 %, 3-23 %, and 9-15 %. Adverse events were reported in 27 % of patients. Reoperation for radiation necrosis occurred in 4 and 27 % of patients following low- and high-dose rate BT, respectively. BT is a feasible option for extending survival in carefully selected GBM patients. As patient outcomes and overall survival improve with more aggressive radiotherapy, so does the risk of radiation-related complications. The most effective use of BT is likely as a part of multimodal treatment with other novel therapies.

Chronic lymphocytic leukemia (CLL) is a malignancy arising from immune cells (B-lymphocytes) endowed with intrinsic antigen-presenting capabilities. Such a function however is lost during malignant transformation and CLL cells are well known for their inability to process and present antigens to the T-cell arm of the immune system. Instead, malignant CLL cells elicit a vast array of immune regulatory mechanisms conducive to T-cell dysfunction and immunosupression. Previously, we have shown that treatment of CLL cells with the demethylating agent 5-aza-2′-deoxycytidine unleashed target antigen expression. Here we show for the first time that combining two epigenetic modifiers, 5-aza-2′-deoxycytidine and the histone deacetylase inhibitor LAQ824 effectively restores the immunogenicity of CLL cell lines as well as primary cells obtained from CLL patients. Indeed, such a combination induces the expression of novel and highly antigenic cancer testis antigens (CTAs) and co-stimulatory molecules. These changes facilitate the formation of robust supramolecular activation complexes (SMAC) between CLL cells and responder T-cells leading to intracellular signaling, lytic granule mobilization, and polarization of functional and relevant T-cell responses. This cascade of T-cell activating events triggered by CLL cells with restored APC function, points to combined epigenetic modifier treatment as a potential immunotherapeutic strategy for CLL patients.