Phase II study of ERC1671 plus bevacizumab versus bevacizumab plus placebo in recurrent glioblastoma: interim results and correlations with CD4+ T-lymphocyte counts.

AIM: ERC1671 is an allogeneic/autologous therapeutic glioblastoma (GBM) vaccine - composed of whole, inactivated tumor cells mixed with tumor cell lysates derived from the patient and three GBM donors. METHODS: In this double-blinded, randomized, Phase II study bevacizumab-naive patients with recurrent GBM were randomized to receive either ERC1671 in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF) (Leukine® or sargramostim) and cyclophosphamide plus bevacizumab, or placebo plus bevacizumab. Interim results: Median overall survival (OS) of patients treated with ERC1671 plus bevacizumab was 12 months. In the placebo plus bevacizumab group, median OS was 7.5 months. The maximal CD4+ T-lymphocyte count correlated with OS in the ERC1671 but not in the placebo group. CONCLUSION: The addition of ERC1671/GM-CSF/cyclophosphamide to bevacizumab resulted in a clinically meaningful survival benefit with minimal additional toxicity.

Spinal cord stimulation for treatment of the pain associated with hereditary multiple osteochondromas.

OBJECTIVE: Hereditary multiple osteochondromas (HMO) usually presents with neoplastic lesions throughout the skeletal system. These lesions frequently cause chronic pain and are conventionally treated with surgical resection and medication. In cases where conventional treatments have failed, spinal cord stimulation (SCS) could be considered as a potential option for pain relief. The objective of this case was to determine if SCS may have a role in treating pain secondary to neoplastic lesions from HMO. CASE PRESENTATION: We report a 65-year-old female who previously received both surgical and pharmacological interventions for treating HMO neoplastic pain in the lumbar, pelvis, femur, and tibial regions. These interventions either failed to offer significant pain relief or caused excessive lethargy. A SCS trial was then offered with a dual 16-contact lead trial leading to 70%-80% improvement in pain from baseline and 85% reduction in oxycodone IR intake. This was followed by permanent implantation of two 2×8 contact paddle leads (T7-T8 and T9-T10 interspaces). After 8-week follow-up, settings were further optimized resulting in an additional 30% improvement in pain compared to last visit. At 6-month follow-up, the patient reported continued pain relief. CONCLUSION: This case demonstrates the first successful use of SCS to treat both HMO and nonmalignant neoplastic-related pain. The patient reported pain improvement from baseline, reduced pain medication requirements, and subjective improvement in quality of life. Additionally, this case demonstrates the potential advantage of trialing multiple painful areas with a 16-contact lead in order to avoid multiple trials and placement.

Hydrogen is neuroprotective against surgically induced brain injury.

BACKGROUND: Neurosurgical operations cause unavoidable damage to healthy brain tissues. Direct surgical injury as well as surgically induced oxidative stress contributes to the subsequent formation of brain edema. Therefore, we tested the neuroprotective effects of hydrogen (H2) in an established surgical brain injury (SBI) model in rats. MATERIALS AND METHODS: Adult male Sprague - Dawley rats (weight 300-350g) were divided into three groups to serve as sham operated, SBI without treatment, and SBI treated with H2 (2.9%). Brain water content, myeloperoxidase (MPO) assay, lipid peroxidation (LPO), and neurological function were measured at 24 hrs after SBI. RESULTS: SBI resulted in localized brain edema (p = < 0.001). Hydrogen (2.9%) administered concurrently with surgery significantly decreased the formation of cerebral edema (p = 0.028) and improved neurobehavioral score (p = 0.022). However, hydrogen treatment failed to reduce oxidative stress (LPO assay) or inflammation (MPO assay) in brain tissues. CONCLUSIONS: Hydrogen appears to be promising as an effective, yet inexpensive way to reduce cerebral edema caused by surgical procedures. Hydrogen has the potential to improve clinical outcome, decrease hospital stay, and reduce overall cost to patients and the health care system.