Prognostic evaluation of re-resection for recurrent glioblastoma using the novel RANO classification for extent of resection: A report of the RANO resect group.

BACKGROUND: The value of re-resection in recurrent glioblastoma remains controversial as a randomized trial that specifies intentional incomplete resection cannot be justified ethically. Here, we aimed to (1) explore the prognostic role of extent of re-resection using the previously proposed Response Assessment in Neuro-Oncology (RANO) classification (based upon residual contrast-enhancing (CE) and non-CE tumor), and to (2) define factors consolidating the surgical effects on outcome. METHODS: The RANO resect group retrospectively compiled an 8-center cohort of patients with first recurrence from previously resected glioblastomas. The associations of re-resection and other clinical factors with outcome were analyzed. Propensity score-matched analyses were constructed to minimize confounding effects when comparing the different RANO classes. RESULTS: We studied 681 patients with first recurrence of Isocitrate Dehydrogenase (IDH) wild-type glioblastomas, including 310 patients who underwent re-resection. Re-resection was associated with prolonged survival even when stratifying for molecular and clinical confounders on multivariate analysis; ≤1 cm3 residual CE tumor was associated with longer survival than non-surgical management. Accordingly, "maximal resection" (class 2) had superior survival compared to "submaximal resection" (class 3). Administration of (radio-)chemotherapy in the absence of postoperative deficits augmented the survival associations of smaller residual CE tumors. Conversely, "supramaximal resection" of non-CE tumor (class 1) was not associated with prolonged survival but was frequently accompanied by postoperative deficits. The prognostic role of residual CE tumor was confirmed in propensity score analyses. CONCLUSIONS: The RANO resect classification serves to stratify patients with re-resection of glioblastoma. Complete resection according to RANO resect classes 1 and 2 is prognostic.

Targeting IL-13Rα2 for effective treatment of malignant peripheral nerve sheath tumors in mouse models.

OBJECTIVEMalignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft tissue sarcomas that harbor a high potential for metastasis and have a devastating prognosis. Combination chemoradiation aids in tumor control and decreases tumor recurrence but causes deleterious side effects and does not extend long-term survival. An effective treatment with limited toxicity and enhanced efficacy is critical for patients suffering from MPNSTs.METHODSThe authors recently identified that interleukin-13 receptor alpha 2 (IL-13Rα2) is overexpressed on MPNSTs and could serve as a precision-based target for delivery of chemotherapeutic agents. In the work reported here, a recombinant fusion molecule consisting of a mutant human IL-13 targeting moiety and a point mutant variant of Pseudomonas exotoxin A (IL-13.E13 K-PE4E) was utilized to treat MPNST in vitro in cell culture and in an in vivo murine model.RESULTSIL-13.E13 K-PE4E had a potent cytotoxic effect on MPNST cells in vitro. Furthermore, intratumoral administration of IL-13.E13 K-PE4E to orthotopically implanted MPNSTs decreased tumor burden 6-fold and 11-fold in late-stage and early-stage MPNST models, respectively. IL-13.E13 K-PE4E treatment also increased survival by 23 days in the early-stage MPNST model.CONCLUSIONSThe current MPNST treatment paradigm consists of 3 prongs: surgery, chemotherapy, and radiation, none of which, either singly or in combination, are curative or extend survival to a clinically meaningful degree. The results presented here provide the possibility of intratumoral therapy with a potent and highly tumor-specific cytotoxin as a fourth treatment prong with the potential to yield improved outcomes in patients with MPNSTs.

Vagal nerve stimulation for medically refractory epilepsy in Angelman syndrome: a series of three cases.

BACKGROUND: We describe three children with Angelman syndrome and medically refractory epilepsy. METHODS: Case series of three pediatric patients with Angelman syndrome and medically refractory epilepsy. All three patients failed medical treatment and were recommended for vagal nerve stimulator (VNS) implantation. RESULTS: Following VNS implantation, all three patients experienced reduction in seizure frequency greater than that afforded by medication alone. CONCLUSION: We present vagal nerve stimulator implantation as a viable treatment option for medically refractory epilepsy associated with Angelman syndrome.

Eliminating unnecessary routine head CT scanning in neurologically intact mild traumatic brain injury patients: implementation and evaluation of a new protocol.

OBJECTIVE The utility of routine repeat head CT (HCT) scans in the management of minimal head injury (MHI) patients with an intracranial hemorrhage (ICH) has been questioned in multiple studies. All these studies analyzed this by obtaining a repeat HCT study, and none examined the effects of eliminating these routine HCT studies in neurologically intact patients. The authors' institution implemented a new "Neurologic Observation without Repeat HCT" (NORH) protocol with no repeat HCT scanning for patients admitted for MHI and ICH whose neurological status was maintained or improved to a Glasgow Coma Scale score of 15 at 24 hours after admission. This purpose of this study was to assess the outcomes and safety of this novel protocol. METHODS Records of patients who sustained blunt trauma MHI and an ICH and/or skull fracture on initial HCT between January 1, 2009, and December 31, 2012, were retrieved from the trauma registry of a Level I trauma center. The authors analyzed 95 patients in whom the NORH protocol was followed. Outcome measures included death, emergency department readmission, neurosurgical intervention, delayed repeat HCT, and length of stay. RESULTS The NORH protocol was followed for 95 patients; 83% of the patients were male, the average age was 38 ± 16.0 years old, and the most common cause of trauma was assault (35%). Of the 95 patients in whom the NORH protocol was followed, 8 (8%) had a delayed repeat HCT study (> 24 hours) after admission, but none resulted in neurosurgical intervention because of progression of ICH. The average length of stay was 4 ± 7.2 days. None of the patients were readmitted to the hospital. CONCLUSIONS Implementation of the NORH protocol (eliminating routine follow-up HCT) resulted in very low rates of delayed neurological deterioration, no late neurosurgical interventions resulting from ICH progression, very few emergency department revisits, and no readmissions. For a select group of MHI patients with ICH, the NORH protocol is safe and effective, and can reduce radiation exposure and costs.

SLAM: Stereotactic Radiosurgery of Large Arteriovenous Malformations: Meta-analysis of Hemorrhage in High-Grade Pollock-Flickinger Arteriovenous Malformations.

BACKGROUND: The prognosis of arteriovenous malformations (AVMs) after treatment has been predicted largely by 2 grading scales: the Spetzler-Martin and Pollock-Flickinger. Although there are studies that examine the rate of hemorrhage with the Spetzler-Martin scale, there have not been studies examining hemorrhage in which the Pollock-Flickinger score was used. The annual hemorrhage rate after radiosurgery of Pollock-Flickinger AVM scores >2 is analyzed. METHODS: Literature search for radiosurgery of large AVMs from January 1, 2000 to June 1, 2014 was conducted. Articles were examined for individual patient data and aggregate patient data that reported hemorrhage rates and mortality. Patients were only included if they had an AVM score ≥2. RESULTS: Annual AVM hemorrhage rate after radiosurgery for all patients (n = 673) was 3.22% (99.3 hemorrhages, 3080.5 follow-up years, 95% confidence interval [95% CI] 2.64%-3.89%). Mortality rate from hemorrhage was 40.08% (95% CI 31.21%-49.90%). A total of 203 patients presented with hemorrhage and 395 did not. In patients with first-time hemorrhage, the annual hemorrhage rate was 3.53% (95% CI 2.66%-4.77%). The annual hemorrhage rate of those with hemorrhagic presentation was 6.10% (95% CI 4.65%-8.07%). The odds ratio comparing re-hemorrhage rate versus first-time hemorrhage is 1.768 (95% CI 1.1571-2.7014, P = 0.0084). Complete obliteration of all AVMs was equal to 33.27% (95% CI, 29.25%-37.54%). CONCLUSIONS: The annual hemorrhage rate in AVMs with scores >2 treated with radiosurgery was comparable with baseline rupture rates reported for untreated AVMs. With further stratification by hemorrhagic versus nonhemorrhagic presentation, the subsequent annual hemorrhage rates are similar to their respective natural histories. Considering the mortality rate from hemorrhage at 40.08% (95% CI, 35.54%-44.62%), the consequences of radiosurgical treatment of large AVMs is significantly worse than the reported 10%-30% fatality rate from hemorrhage of an untreated AVM. Additionally, the overall mortality rate was 6.24% however the percentage of mortalities from hemorrhage was 97.62%.