Emerging and investigational targeted chemotherapy and immunotherapy agents for metastatic brain tumors.

INTRODUCTION: Metastases to the central nervous system are the most common cause of malignant intracranial tumors in adults. Current standard of care includes surgery and radiation, but overall survival remains poor. A range of systemic therapies are emerging as promising treatment options for these patients. AREAS COVERED: This study reviews novel drug regimens that are under investigation in phase 1 and 2 clinical trials. To identify relevant therapies under clinical investigation, a search was performed on http://clinicaltrials.gov and Pubmed with the keywords brain metastasis, Phase I clinical trial, and Phase II clinical trial from 2016 to 2020. The authors detail the mechanisms of action of all trial agents, outline evidence for their utility, and summarize the current state of the field. EXPERT OPINION: Current advancements in the medical management of brain metastases can be categorized into targeted therapies, methods of overcoming treatment resistance, novel combinations of therapies, and modulation of the tumor microenvironment with a specific focus on immunotherapy. Each of these realms holds great promise for the field going forward. A more streamlined structure for enrollment into clinical trials will be a crucial step in accelerating progress in this area.

Evaluation of Heterotopic Ossification After Using Recombinant Human Bone Morphogenetic Protein-2 in Transforaminal Lumbar Interbody Fusion: A Computed Tomography Review of 996 Disc Levels.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: Reported incidences and complications of heterotopic ossification (HO) after using recombinant human bone morphogenetic protein-2 (rhBMP-2) in transforaminal lumbar interbody fusion (TLIF) have been inconclusive. This study was designed to evaluate both incidences of radiologic and symptomatic HO in a large series of TLIFs using rhBMP-2. METHODS: A total of 996 disc levels in 927 consecutive TLIF patients were retrospectively evaluated at 6-month postoperative follow-up in a single surgical practice. Subjects were separated into the BMP group and the control group. Operative reports, pre- and postoperative medical records were reviewed. Computed tomography (CT) scans were analyzed and graded independently for ossification at each disc level of TLIF. RESULTS: A total of 933 disc levels were in the BMP group, and 63 were in the control group. Six-month fusion rate of interbody was 92.5% in the BMP group, which was significantly higher in contrast to 71.4% in the control group (P < .001). The incidence of radiologic HO in the BMP group was 13.5%, which was significantly higher than 1.6% in the control group (P = .006). After controlling for basic demographics and comorbidities, the presence of radiologic HO was significantly associated with the use of rhBMP-2 (P = .026). However, only one case in the BMP group (0.11%) developed a symptomatic HO (mild-medium left buttock pain, treated nonsurgically) involving left foramen of L5-S1. CONCLUSIONS: rhBMP-2 can be safely used in TLIF with regard to HO. There was a low rate of radiologic HO and minimal symptomatic HO, with high fusion rates at 6 months postoperative.

The Frequency of Various "Myelopathic Symptoms" in Cervical Myelopathy: Evaluation in a Large Surgical Cohort.

STUDY DESIGN: A retrospective cohort of prospective data. OBJECTIVE: Determine the frequency of various symptoms in a surgical cohort of cervical myelopathy (CM). SUMMARY OF BACKGROUND DATA: CM can be difficult to diagnose as there is no sine qua non "myelopathic symptom." Despite extensive literature, the likelihood or frequency of symptoms at presentation remains unclear. MATERIALS AND METHODS: A total of 484 patients treated at a single academic center were reviewed. Preoperative symptoms included: axial neck pain; upper extremity (UE) pain; UE sensory or motor deficit; lower extremity (LE) sensory or motor deficit; and sphincter dysfunction. It was noted whether a symptom was the chief complaint (CC) and/or one of a list of overall symptoms (OS) reported by the patient. Magnetic resonance imaging was assessed for the maximal cord compression level and T2 hyperintensity. RESULTS: The most common CC was UE sensory deficit (46.5%), whereas the most common OS were UE and LE motor deficits (82.6% and 81.2%). Neck pain was significantly less common (32.6% CC, 55.4% OS), and sphincter dysfunction was rare (0.6% CC, 16.5% OS). UE pain as a CC was significantly higher when the maximal compression involved a more distal level. The presence of T2 hyperintensity was negatively associated with neck pain but positively associated with sensory and motor deficits of LE. CONCLUSIONS: The most common CC in CM related to UE sensation, whereas the most common OS related to upper and lower motor function. UE pain was more common with more distal cord compression. Those with T2 hyperintensity had worse myelopathy and were less likely to have neck pain, but more likely to have LE symptoms. To our knowledge, this study is the largest to quantify the frequency of myelopathic symptom presentation in a surgical population. These findings provide valuable insight into the symptomatic presentation of CM in clinical practice and can be used to better inform diagnosis and treatment in this complex patient population. LEVEL OF EVIDENCE: Level II-retrospective study.