Faculty Bibliography

OBJECTIVE:The goal of this study was to describe the clinical presentation associated with atypical schwannoma of the cerebellopontine angle, characterize the pathologic findings and describe the long-term outcome. MATERIALS AND METHODS/METHODS:The study design was retrospective case review of patients with the histopathologic diagnosis of atypical and benign schwannoma of the cerebellopontine angle diagnosed at the study institution over a 10-year period. SETTING/METHODS:Tertiary referral center. MAIN OUTCOMES MEASURE/METHODS:Demographic data of the cohort were recorded. Findings on pathology were evaluated. Initial treatment and post-operative course was recorded. Main outcome measures were clinical presentation, including cranial nerve deficits at the time of presentation, complication and recurrence rates. RESULTS:At presentation, a somewhat accelerated course of cranial nerve deficit was noted among patients with atypical schwannoma as compared to benign schwannoma. In the immediate post-operative period, there were no differences noted in the complication rate. Atypical schwannomas appear to have higher recurrence rate compared to benign schwannomas. CONCLUSIONS:Atypical schwannoma is an intermediate disease process with an accelerated clinical course and higher recurrence rate as compared to vestibular schwannoma. Traditional operative approaches may be employed without increased concern for post-operative complications. Thorough counseling and close follow-up should be offered to these patients given the higher recurrence rate. Larger studies are required to determine if these patients need more frequent MRIs for long-term surveillance.

BACKGROUND: There is no effective therapy for patients (pts) with IDH-mutant gliomas that progress after RT and chemotherapy. At time of progression, these tumors have often transformed to glioblastoma (GBM) and have increased numbers of somatic mutations, i.e. have a ?hypermutator phenotype?. We hypothesized that there is synergistic efficacy of Avelumab (anti-PD-L1) combined with HFRT in pts with secondarily trans- formed IDH-mutant GBMs. Safety-lead-in results will be presented.
METHOD(S): This is a phase II, open-label, single-arm, multicenter study of Avelumab with HFRT in adults with transformed IDH-mutant GBM who previously received RT and TMZ and/or PCV. All pts received Avelumab 10 mg/kg IV followed at Day 8 by HFRT (25 Gy in 5 daily 5-Gy fractions) and then Avelumab 10 mg/kg IV every 2 weeks. A 3 + 3 design was used for a 6-patient safety-lead-in cohort. Adverse events were recorded according to CTCAE.
RESULT(S): Six pts (F=4, M=2) with a median age= 45.5 yrs (range 31.5-54.4 yrs) were enrolled in the safety-lead-in cohort. No DLT was observed. Grade >= 3 AEs included increased cerebral edema (3 pts), hyponatremia (1 pt) and worsening hemiparesis (3 pts). Grade <= 2 AEs included nausea, hypothyroidism, lymphopenia, thrombocytopenia, transaminase elevation, and fever/chills. Median follow-up time was 8.9 mo. Best treatment response was SD in 1 patient. At time of last follow-up all pts have discontinued treatment for PD. Median PFS was 4.2 mo (range 1.4-5.7). Median OS was 10.1 (range 6.8-21+) mo. 4 pts (67%) died, 2 pts remain alive in follow-up at 6.9 and 21.6 months after treatment initiation. The study was closed after the safety lead-in completed enrollment due to slow accrual.
CONCLUSION(S): Avelumab combined with HFRT was tolerable without dose-limiting toxicity in this safety-lead-in cohort of adult patients with transformed IDH-mutant GBM. Further studies are necessary to determine efficacy of this treatment regimen

IDH1/2 mutations are early drivers present in diverse human cancer types arising in various tissue sites. IDH1/2 mutation is known to induce a global hypermethylator phenotype. However, the effects on DNA methylation across IDH mutant cancers and functionally different genome regions, remain unknown. We analyzed DNA methylation data from IDH1/2 mutant acute myeloid leukemia, oligodendroglioma, astrocytoma, solid papillary breast carcinoma with reverse polarity, sinonasal undifferentiated carcinoma and cholangiocarcinoma, which clustered by their embryonal origin. Hypermethylated common probes affect predominantly gene bodies while promoters in IDH1/2 mutant cancers remain unmethylated. Enhancers showed global hypermethylation, however commonly hypomethylated enhancers were associated with tissue differentiation and cell fate determination. We demonstrate that some chromosomes, chromosomal arms and chromosomal regions are more affected by IDH1/2 mutations while others remain resistant to IDH1/2 mutation induced methylation changes. Therefore IDH1/2 mutations have different methylation effect on different parts of the genome, which may be regulated by different mechanisms.

Following publication of the original article [1], it was reported that the given name of the fourteenth author was incorrectly published. The incorrect and the correct names are given below.

OBJECTIVE:The most common functioning pituitary adenoma is prolactinoma. Patients with medically refractory or residual/recurrent tumors that are not amenable to resection can be treated with stereotactic radiosurgery (SRS). The aim of this multicenter study was to evaluate the role of SRS for treating prolactinomas. METHODS:This retrospective study included prolactinomas treated with SRS between 1997 and 2016 at ten institutions. Patients' clinical and treatment parameters were investigated. Patients were considered to be in endocrine remission when they had a normal level of prolactin (PRL) without requiring dopamine agonist medications. Endocrine control was defined as endocrine remission or a controlled PRL level ≤ 30 ng/ml with dopamine agonist therapy. Other outcomes were evaluated including new-onset hormone deficiency, tumor recurrence, and new neurological complications. RESULTS:The study cohort comprised 289 patients. The endocrine remission rates were 28%, 41%, and 54% at 3, 5, and 8 years after SRS, respectively. Following SRS, 25% of patients (72/289) had new hormone deficiency. Sixty-three percent of the patients (127/201) with available data attained endocrine control. Three percent of patients (9/269) had a new visual complication after SRS. Five percent of the patients (13/285) were recorded as having tumor progression. A pretreatment PRL level ≤ 270 ng/ml was a predictor of endocrine remission (p = 0.005, adjusted HR 0.487). An increasing margin dose resulted in better endocrine control after SRS (p = 0.033, adjusted OR 1.087). CONCLUSIONS:In patients with medically refractory prolactinomas or a residual/recurrent prolactinoma, SRS affords remarkable therapeutic effects in endocrine remission, endocrine control, and tumor control. New-onset hypopituitarism is the most common adverse event.