Leila A. Mashouf

Improvements in bioengineering methodology and tools have allowed for significant progress in the development of therapeutics and diagnostics in medicine, as well as progress in many other diverse industries, such as materials manufacturing, food and agriculture, and consumer goods. Glioblastomas present significant challenges to adequate treatment, in part due to their immune-evasive and manipulative nature. Rational-design bioengineering using novel scaffolds, biomaterials, and inspiration across disciplines can push the boundaries in treatment development to create effective therapeutics for glioblastomas. In this review, we will discuss bioengineering strategies currently applied across diseases and disciplines to inspire creative development for GBM immunotherapies.

Microvascular decompression (MVD) is an established procedure for treating conditions such as trigeminal neuralgia and hemifacial spasm. However, during a standard retrosigmoid approach, the decision to sacrifice the superior petrosal vein (SPV) is controversial. There have been multiple reports of complications including life-threatening brainstem infarction and cerebellar edema. This study analyzes the potential for vascular complications when the SPV is sacrificed during an MVD. Retrospective chart review was performed to identify all MVDs from 2007 to 2018 by the senior author. Cases with >1 mo of follow-up were included and sacrifice of the SPV or its branches was noted. The primary outcome was complications related to SPV sacrifice including sinus thrombosis, cerebellar edema, and midbrain or pontine infarction. Imaging was used to confirm all potential vascular complications mentioned in clinical notes. Fisher's exact test and unpaired t-tests were used to compare between groups. A total of 701 MVD cases were identified and 570 met inclusion criteria with an average follow-up of 12.0 ± 16.7 mo and a male-to-female ratio of 1:2.1. A total of 141 patients (24.7%) had previous interventions and 10 patients had previous ipsilateral MVDs. The SPV was sacrificed in 211 cases and retained in 359 cases. At final follow-up, 149 patients (70.6%) were pain-free in the group with the sacrificed vein and 240 patients (66.9%) were pain-free in the nonsacrificed group (P = .402). No SPV-related vascular complications were found in this study. Two unrelated cases of vascular complications were identified and both were in the nonsacrificed group. One case involved cerebellar bleeding while the other was an ipsilateral transverse sinus thrombosis that was present preoperatively. In MVDs, there is no difference in rate of vascular complications when the SPV is sacrificed compared to preserved. To best visualize a cranial nerve and optimize safe decompression, surgeons should feel free to resect the SPV.

Brain metastases are common in patients with advanced systemic cancer and often recur despite treatment with surgical resection and radiotherapy. Whole brain radiation therapy (WBRT) and stereotactic radiosurgery (SRS) have significantly improved local control rates but are limited by complications including neurocognitive deficits and radiation necrosis. These risks can be higher in the re-irradiation setting. Brachytherapy may be an alternative method of additional targeted adjuvant radiotherapy with acceptable rates of toxicity. A retrospective chart review of all patients undergoing resection for metastatic brain lesions and permanent low-dose rate Cs-131 brachytherapy was performed for one institution over a 10-year period. All patients had previous radiation therapy already and, after surgery, were followed with imaging every three months. Patient demographics, disease characteristics, intracranial disease, peri- and post-operative complications, and outcomes were recorded. The primary outcome of interest was local tumor recurrence at the site of brachytherapy while secondary outcomes included distant disease progression (within the brain) and complications such as radiation necrosis. During the study period, nine cases of individual patients met inclusion criteria. The median preoperative lesion diameter was 3 cm (0.8–4.1). The median overall survival after surgery and brachytherapy was 10.3 months, after excluding two patients who were lost to follow-up. Six of nine patients had no local recurrence, while three patients had development or progression of distant lesions. No patients experienced acute or delayed complications. Cs-131 brachytherapy is a promising alternative method for controlling brain metastases after previous radiation interventions and surgical resection. In this case series, there were no incidences of local tumor recurrence or complications such as radiation necrosis.

Patients with melanoma can present with a hemorrhagic intracranial lesion. Upon resection, pathology reports may not detect any malignant cells. However, the hemorrhage may obscure their presence and so physicians may still decide whether adjuvant radiotherapy should be applied. Here, we report on the outcomes of a series of patients with melanoma with hemorrhagic brain lesions that returned with no tumor cells. All melanoma patients who had craniotomies from 2008 to 2017 at a single institution for hemorrhagic brain lesions were identified through retrospective chart review. Those who had pathology reports with no malignant cells were analyzed. Recurrence at the former site of hemorrhage and resection was the primary outcome. Ten patients met inclusion criteria, and the median follow-up time was 8.5 (1.8-27.3) months. At the time of craniotomy, the median number of brain lesions was 3 (1-25). Two patients had prior craniotomies, eight had prior radiation, and six had prior immunotherapy to the lesion of interest. After surgery, one patient received stereotactic radiosurgery (SRS) to the resection bed. Only one patient developed subsequent melanoma at the resection site; this patient developed the lesion recurrence once and had not received postoperative SRS. Although small foci of metastatic disease as a source of bleeding for some patients cannot be excluded, melanoma patients with a suspected hemorrhagic brain metastasis that shows no tumor cells on pathology may benefit from close observation. The local recurrence risk in such cases appears to be low, even without adjuvant radiation.