Marks, Lisa A.

Alternating electrical fields can disrupt mitosis leading to apoptosis of rapidly dividing cancer cells. The device that utilizes this mechanism is known as tumor-treating fields (TTFields). TTFields can be applied by ceramic transducer arrays on a shaved scalp to deliver the alternating electric activity to patients with glioblastoma (GBM). It has FDA approval for use in both recurrent and newly diagnosed GBM. The objective is to critically appraise the current evidence for the use of TTFields as adjunctive treatment to newly diagnosed GBM. The objective was addressed through the development of a structured, critically appraised topic. We incorporated a clinical scenario, background information, a structured question, literature search strategy, evidence summary, clinical bottom lines, and expert discussion. Participants included consultant and resident neurologists, a medical librarian, clinical epidemiologists, and content experts in the field of neurooncology. A randomized controlled trial was selected for critical appraisal. Patients with newly diagnosed GBM completing standard radiation and chemotherapy with temozolomide (TMZ) were subsequently randomized to receive maintenance TMZ with TTFields, or TMZ alone. With the addition of TTFields, median progression-free survival was 6.7 months compared with 4 months without the addition of TTFields (95% confidence interval, 0.52-0.76; P<0.001) and overall survival was 20.9 months compared with 16.0 months without the addition of TTFields (95% confidence interval, 0.53-0.76; P<0.001). TTFields may increase both progression-free and overall survival in patients receiving standard chemoradiation therapy for GBM.

Mechanical thrombectomy (MT) is the standard of care for patients who present with an acute ischemic stroke within 6 hours of symptom onset, and up to 24 hours in appropriately selected patients. However, optimal postoperative management of these patients remains uncertain, especially with regard to blood pressure control. To review the existing literature to define potential blood pressure goals in the immediate postoperative period in patients who undergo MT for acute ischemic stroke. The topic was defined through a clinical scenario and the subsequent development of a targeted clinical question. A literature search was performed, with relevant articles selected, one of which, a prospective observational study, was critically appraised. Participants included neurology residents and consultants, a medical librarian, clinical epidemiologists, as well as content experts from vascular neurology and interventional neuroradiology. Permissive hypertension (defined as <220/120 or <180/105 mm Hg as per the American Heart Association/American Stroke Association guidelines) may be harmful in the postoperative period following MT, especially in patients who were successfully recanalized. Moderate blood pressure control (<160/90) was found to be a predictor of improved 3-month mortality on multivariable logistic regression analysis in patients who sustained successful reperfusion [odds ratio (OR), 0.08; 95% confidence interval (CI), 0.01-0.054; P=0.01]. A 10 mm Hg increase in systolic blood pressure was found to result in a lower OR of having a favorable 3-month functional independence (OR, 0.70; 95% CI, 0.56-0.85; P=0.001) as well as higher rates of 3-month mortality (OR, 1.49; 95% CI, 1.18-1.88; P=0.001). Blood pressure goals in the immediate postoperative period in patients who undergo MT should differ than those who do not undergo MT, with data suggesting that lower blood pressure than permissive hypertension may be related to improved outcomes, especially in cases of successful reperfusion. However, current data are derived from observational studies; further studies, preferably in the form of randomized-controlled trials, are needed to further clarify the relationship between postoperative blood pressures and outcomes in this patient population.