Publications by authors named "Ian E McCutcheon"

105 Publications

Comparison of Cancer Prevalence in Patients With Neurofibromatosis Type 1 at an Academic Cancer Center vs in the General Population From 1985 to 2020.

JAMA Netw Open 2021 Mar 1;4(3):e210945. Epub 2021 Mar 1.

Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston.

Importance: Neurofibromatosis type 1 (NF1) is a complex genetic disorder that is associated with not only neurofibromas, but also an increased susceptibility to other neoplasms.

Objective: To evaluate the prevalence of neoplasia and outcomes among patients with NF1.

Design, Setting, And Participants: This cohort study was conducted among patients with NF1 at a single academic cancer center from 1985 to 2020 with median (range) follow-up of 2.9 years (36 days to 30.5 years). Of 2427 patients evaluated for NF1, 1607 patients who met the National Institutes of Health consensus criteria for NF1 were included. This group was compared with estimates from Surveillance, Epidemiology, and End Results (SEER) Cancer Statistics Review 1975 to 2015 and SEER participants database unless otherwise specified. Data were analyzed from August 2018 to March 2020.

Main Outcomes And Measures: Disease-specific survival (DSS) was measured from diagnosis date to date of neoplasm-specific death or censorship and calculated using the Kaplan-Meier method. Survival curves were compared using the log-rank test. Deaths from disease were considered a DSS end point; other deaths were considered censored observations. Secondary outcome measures were comparisons of (1) overall survival of patients with NF1 with neurofibroma neoplasms vs those without nonneurofibroma neoplasms, (2) neoplasm prevalence in the NF1 group vs general population estimates, and (3) age at diagnosis in the NF1 group vs general population estimates for the most common neoplasms in the NF1 group.

Results: Among 1607 patients with NF1, the median (range) age at initial visit was 19 years (1 month to 83 years) and 840 (52.3%) were female patients. Among 666 patients who developed other neoplasms in addition to neurofibromas (41.4%), 295 patients (18.4%) developed glioma and 243 patients (15.1%) developed malignant peripheral nerve sheath tumor (MPNST), the most common neoplasms. Patients with NF1, compared with the general population, developed several neoplasms at a younger mean (SD) age (low-grade glioma: 12.98 [11.09] years vs 37.76 [24.53] years; P < .0001; high-grade glioma [HGG]: 27.31 [15.59] years vs 58.42 [19.09] years; P < .0001; MPNST: 33.88 [14.80] years vs 47.06 [20.76] years; P < .0001; breast cancer: 46.61 [9.94] years vs 61.71 [13.85] years; P < .0001). Patients with NF1 developed neoplasms more frequently compared with the general population (odds ratio, 9.5; 95% CI, 8.5-10.5; P < .0001). Among patients with NF1, significantly lower 5-year DSS rates were found among those with undifferentiated pleomorphic sarcoma (1 of 5 patients [20.0%]), HGG (8 of 34 patients [23.1%]), MPNST (72 of 228 patients [31.6%]), ovarian carcinoma (4 of 7 patients [57.1%]), and melanoma (8 of 12 patients [66.7%]) compared with those who had neoplasms classified as other (110 of 119 patients [92.4%]) (all P < .001) .

Conclusions And Relevance: This cohort study found that among patients with NF1, those who developed undifferentiated pleomorphic sarcoma, HGG, MPNST, ovarian carcinoma, or melanoma had significantly lower DSS rates compared with those who developed other neoplasms. This study also found that patients with NF1 developed some neoplasms more frequently and at a younger age compared with individuals without NF1. HGGs and MPNST were noteworthy causes of death among patients NF1. This information may be useful for NF1 patient counseling and follow-up.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.0945DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7974640PMC
March 2021

Historical Perspective on Surgery and Survival with Glioblastoma: How Far Have We Come?

World Neurosurg 2021 May 19;149:148-168. Epub 2021 Feb 19.

The Loyal and Edith Davis Neurosurgical Research Laboratory, Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona, USA. Electronic address:

Background: Glioblastoma multiforme remains a therapeutic challenge. We offer a historical review of the outcomes of patients with glioblastoma from the earliest report of surgery for this lesion through the introduction of modern chemotherapeutics and aggressive approaches to tumor resection.

Methods: We reviewed all major surgical series of patients with glioblastoma from the introduction of craniotomy for glioma (1884) to 2020.

Results: The earliest reported craniotomy for glioblastoma resulted in the patient's death less than a month after surgery. Improved intracranial pressure management resulted in improved outcomes, reducing early postoperative mortality from 50% to 6% in Harvey Cushing's series. In the first major surgical series (1912), the mean survival was 10.1 months. This figure did not improve until the introduction of radiotherapy in the 1950s, which doubled survival relative to those who had surgery alone. The most recent significant advance, chemotherapy with the alkylating agent temozolomide, extended survival by 2.5 months compared with surgery and radiotherapy alone (14.6 and 12.1 months, respectively). This protocol remains the standard regimen for newly diagnosed glioblastoma. The innovative treatments being investigated have yet to show a survival benefit.

Conclusions: With advancements in localization, imaging, anesthesia, surgical technique, control of cerebral edema, and adjuvant therapies, outcomes in glioblastoma improved incrementally from Cushing's time until the introduction of magnetic resonance imaging enabled better degrees of resection in the 1990s. Modest improvements came with the advent of biomarker-driven targeted chemotherapy in the first decade of the current century.
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http://dx.doi.org/10.1016/j.wneu.2021.02.047DOI Listing
May 2021

Efficacy of pembrolizumab in patients with pituitary carcinoma: report of four cases from a phase II study.

J Immunother Cancer 2020 12;8(2)

Department of Investigational Cancer Therapeutics, University of Texas at MD Anderson Cancer Center, Houston, Texas, USA

Pituitary carcinoma is an aggressive tumor characterized by metastatic spread beyond the sellar region. Symptoms can be debilitating due to hormonal excess and survival is poor. Pituitary carcinomas recur despite conventional multimodality treatments. Given the recent advances in the use of immune checkpoint inhibitors (CPIs) to treat various solid cancers, there has been interest in exploring the role of immunotherapy for treating aggressive, refractory pituitary tumors. We treated 4 patients with pituitary carcinoma with pembrolizumab as part of a phase II clinical trial. Two patients (patients 1 and 2) with functioning corticotroph pituitary carcinomas (refractory to surgery, radiotherapy and chemotherapy) had partial radiographic (60% and 32% per Immune-Related Response Evaluation Criteria In Solid Tumors, respectively) and hormonal responses. Patient 1's response continues 42 months after initiation of pembrolizumab and his tumor tissue obtained after treatment with temozolomide demonstrated a hypermutator phenotype with and gene mutations. Patient 2's tumor after exposure to temozolomide was not sampled, but prior somatic mutational testing was negative. One patient with a non-functioning corticotroph tumor (patient 3) had a best response of stable disease for 4 months. One patient with a prolactin-secreting carcinoma (patient 4) had progressive disease. The latter 2 patients' tumors did not demonstrate a hypermutator phenotype after treatment with temozolomide. Programmed death-ligand 1 staining was negative in all tumors. We report 2 cases of corticotroph pituitary carcinoma responsive to pembrolizumab after prior exposure to alkylating agents. The role of CPIs in treating patients with pituitary carcinoma, the relationship between tumor subtype and response to immunotherapy and mechanisms of hypermutation in this orphan disease require further study.Trial registration number: NCT02721732.
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http://dx.doi.org/10.1136/jitc-2020-001532DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7757504PMC
December 2020

Stereotactic Radiosurgery Hypophysectomy for Palliative Treatment of Refractory Cancer Pain: A Historical Review and Update.

Front Oncol 2020 17;10:572557. Epub 2020 Dec 17.

Department of Neurosurgery, Baylor College of Medicine, Houston, TX, United States.

Medically refractory pain in those with advanced cancer significantly reduces one's quality of life. Therefore, palliative interventions to mitigate cancer pain and reduce opioid requirements are necessary to reduce patient suffering and opioid-induced side effects. Hypophysectomy, a largely forgotten pain procedure with several technical variations, has been repeatedly studied in small series with encouraging results, though historically has been fraught with complications. As a result, the minimally invasive and more tolerable stereotactic radiosurgery (SRS) hypophysectomy has resurfaced as a possible treatment for cancer-related pain. While the mechanism of pain relief is not entirely understood, the hypothalamohypophyseal axis appears to play an essential role in pain perception and transmission and involves C fiber signal processing and downstream modulation of the brainstem and spinal cord the hypothalamus. This review highlights the role of hypophysectomy in alleviating advanced cancer pain, both in hormonal and nonhormonal malignancy and the current mechanistic understanding of pain relief for the three primary hypophysectomy modalities used historically: surgical and chemical adenolysis, as well as the more recent, SRS hypophysectomy. Given the lack of high-quality evidence for stereotactic radiosurgery hypophysectomy, there is a need for further rigorous and prospective clinical studies despite its ideal and noninvasive approach.
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http://dx.doi.org/10.3389/fonc.2020.572557DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7773820PMC
December 2020

Window-of-opportunity clinical trial of pembrolizumab in patients with recurrent glioblastoma reveals predominance of immune-suppressive macrophages.

Neuro Oncol 2020 04;22(4):539-549

Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Background: We sought to ascertain the immune effector function of pembrolizumab within the glioblastoma (GBM) microenvironment during the therapeutic window.

Methods: In an open-label, single-center, single-arm phase II "window-of-opportunity" trial in 15 patients with recurrent (operable) GBM receiving up to 2 pembrolizumab doses before surgery and every 3 weeks afterward until disease progression or unacceptable toxicities occurred, immune responses were evaluated within the tumor.

Results: No treatment-related deaths occurred. Overall median follow-up time was 50 months. Of 14 patients monitored, 10 had progressive disease, 3 had a partial response, and 1 had stable disease. Median progression-free survival (PFS) was 4.5 months (95% CI: 2.27, 6.83), and the 6-month PFS rate was 40%. Median overall survival (OS) was 20 months, with an estimated 1-year OS rate of 63%. GBM patients' recurrent tumors contained few T cells that demonstrated a paucity of immune activation markers, but the tumor microenvironment was markedly enriched for CD68+ macrophages.

Conclusions: Immune analyses indicated that pembrolizumab anti-programmed cell death 1 (PD-1) monotherapy alone can't induce effector immunologic response in most GBM patients, probably owing to a scarcity of T cells within the tumor microenvironment and a CD68+ macrophage preponderance.
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http://dx.doi.org/10.1093/neuonc/noz185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7158647PMC
April 2020

Commentary: Rare Primary Embryonal Carcinoma in the Brachial Plexus: A Case Report and Literature Review.

Authors:
Ian E McCutcheon

Neurosurgery 2020 08;87(2):E156-E157

Department of Neurosurgery, The University of Texas M.D. Anderson Cancer Center, Houston, Texas.

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http://dx.doi.org/10.1093/neuros/nyz469DOI Listing
August 2020

Introduction. Primary and secondary infections of the brain.

Neurosurg Focus 2019 08;47(2):E1

3Department of Neurosurgery, The University of Texas M. D. Anderson Cancer Center, Houston, Texas.

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http://dx.doi.org/10.3171/2019.5.FOCUS19390DOI Listing
August 2019

Treatment and long-term outcomes in pituitary carcinoma: a cohort study.

Eur J Endocrinol 2019 Oct;181(4):397-407

Department of Neurosurgery, MD Anderson Cancer Center, Houston, Texas, USA.

Background: Pituitary carcinoma (PC) is an aggressive neuroendocrine tumor diagnosed when a pituitary adenoma (PA) becomes metastatic. PCs are typically resistant to therapy and develop multiple recurrences despite surgery, radiotherapy and chemotherapy. Recently, treatment with temozolomide (TMZ) has shown promising results, although the lack of prospective trials limits assessment of benefit.

Methods: We describe a single-center multidisciplinary experience in managing PC patients over a 22-year period and review previously published PC series.

Results: Seventeen patients were identified. Median age at PC diagnosis was 44 years (range 16-82 years), and the median time from PA to PC transformation was 5 years (range 1-29 years). Median follow-up time was 28 months. Most PCs were hormone-positive (n = 12): ACTH (n = 5), PRL (n = 4), LH/FSH (n = 2) and GH (n = 1). All patients underwent at least one resection and at least one course of radiation after PC diagnosis. Immunohistochemistry showed high Ki-67 labeling index (>3%) in 10/15 cases. Eight patients (47%) had only central nervous system (CNS) metastases; six (35%) had combined CNS and systemic metastases. The most commonly used chemotherapy was TMZ, and TMZ-based therapy was associated with the longest PFS in 12 (71%) cases, as well as the longest period from PC diagnosis to first progression (median 30 months). The 2, 3 and 5-year survival rate of the entire cohort was 71, 59 and 35%, respectively. All patients surviving >5 years had been treated with TMZ-based therapy.

Conclusions: PC management benefits from multidisciplinary care and multimodality therapy. TMZ-based regimens were associated with high survival rates and long disease control.
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http://dx.doi.org/10.1530/EJE-18-0795DOI Listing
October 2019

Predictors of survival in metastatic melanoma patients with leptomeningeal disease (LMD).

J Neurooncol 2019 May 7;142(3):499-509. Epub 2019 Mar 7.

Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Purpose: Although the survival of most melanoma patients diagnosed with leptomeningeal disease (LMD) is short, some patients can have better outcomes and prolonged survival. A large retrospective cohort of patients was analyzed to identify features associated with survival with LMD from melanoma.

Methods: Clinical characteristics, treatments and survival were collected for melanoma patients diagnosed with LMD from 1999 to 2015. The Kaplan-Meier method was used to estimate overall survival (OS) and Cox proportional hazards regression was used to test statistical significance of associations with survival. Multivariate analysis was performed using Cox proportional regression modeling.

Results: 178 melanoma patients with LMD were identified. Median age at LMD diagnosis was 51 years. Most (n = 153) patients received at least one treatment for LMD, including radiation (n = 98), chemotherapy (n = 89), targeted therapy (n = 60), immunotherapy (n = 12), or intrathecal (IT) therapy (n = 64). Median OS from LMD diagnosis was 3.5 months. One-, two-, and five-year OS rates were 22%, 14%, and 9%, respectively. Factors significantly associated with OS on multivariate analysis included Eastern Cooperative Oncology Group [ECOG] performance status > 0 (HR 2.1, P < 0.0001); neurological symptoms (HR 1.6, P < 0.0001); absent systemic disease (HR 0.4, P < 0.0001); and LMD treatment (HR 0.4, P = 0.0024), targeted therapy (HR 0.6, P = 0.0060), or IT therapy (HR 0.5, P = 0.0019).

Conclusion: Despite their overall poor prognosis a subset of melanoma patients with LMD achieve longer survival. The factors associated with outcomes may be used to guide patient management and to inform the design of future clinical trials for this population.
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http://dx.doi.org/10.1007/s11060-019-03121-2DOI Listing
May 2019

Perilesional Resection of Glioblastoma Is Independently Associated With Improved Outcomes.

Neurosurgery 2020 01;86(1):112-121

Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Background: Resection is a critical component in the initial treatment of glioblastoma (GBM). Often GBMs are resected using an intralesional method. Circumferential perilesional resection of GBMs has been described, but with limited data.

Objective: To conduct an observational retrospective analysis to test whether perilesional resection produced a greater extent of resection.

Methods: We identified all patients with newly diagnosed GBM who underwent resection at our institution from June 1, 1993 to December 31, 2015. Demographics, presenting symptoms, intraoperative data, method of resection (perilesional or intralesional), volumetric imaging data, and postoperative outcomes were obtained. Complete resection (CR) was defined as 100% resection of all contrast-enhancing disease. Univariate analyses employed analysis of variance (ANOVA) and Fisher's exact test. Multivariate analyses used propensity score-weighted multivariate logistic regression.

Results: Newly diagnosed GBMs were resected in 1204 patients, 436 tumors (36%) perilesionally and 766 (64%) intralesionally. Radiographic CR was achieved in 69% of cases. Multivariate analysis demonstrated that perilesional tumor resection was associated with a significantly higher rate of CR than intralesional resection (81% vs 62%, multivariate odds ratio = 2.5, 95% confidence interval: 1.8-3.4, P < .001). Among tumors in eloquent cortex, multivariate analysis showed that patients who underwent perilesional resection had a higher rate of CR (79% vs 58%, respectively, P < .001) and a lower rate of neurological complications (11% vs 20%, respectively, P = .018) than those who underwent intralesional resection.

Conclusion: Circumferential perilesional resection of GBM is associated with significantly higher rates of CR and lower rates of neurological complications than intralesional resection, even for tumors arising in eloquent locations. Perilesional resection, when feasible, should be considered as a preferred option.
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http://dx.doi.org/10.1093/neuros/nyz008DOI Listing
January 2020

Association between intravenous acetaminophen and reduction in intraoperative opioid consumption during transsphenoidal surgery for pituitary tumors.

J Anaesthesiol Clin Pharmacol 2018 Oct-Dec;34(4):465-471

Anesthesiology and Surgical Oncology Research Group, Houston, Texas, USA.

Background And Aims: Pain during and after transsphenoidal surgeries originates from stimulation of branches of the trigeminal cranial nerve that supply the inner aspect of the nose cavity and dura mater. Thereby, patients undergoing transsphenoidal surgery may require moderate-to-large amounts of analgesics including opioids. Intravenous acetaminophen provides analgesia and reduces opioid consumption for a wide variety of surgeries. We hypothesized that the use of intravenous acetaminophen is associated with a reduction in intraoperative opioid consumption and provides significant analgesia during and after transsphenoidal surgery.

Material And Methods: This retrospective study included 413 patients who underwent transsphenoidal surgery for pituitary adenomas. The primary outcome of this study was intraoperative opioid consumption. Secondary outcomes included pain intensity, Richmond Agitation Sedation Scale scores, and nausea and vomiting upon arrival to postoperative anesthesia care unit. Patients were divided into two groups based on the intraoperative acetaminophen use. A prospensity score matching analysis was used to balance for important variables between the two groups of treatment. Regression models were fitted after matching the covariates. A < 0.05 was considered statistically significant.

Results: After matching, 126 patients were included in each group of treatment. Patients in the acetaminophen group required significantly less amount (a decrease by 14.9%) of opioids during surgery than those in the non-acetaminophen group. Postoperative pain, postoperative nausea and vomiting, and sedation scores were not significantly different between patients who received intravenous acetaminophen and those who did not.

Conclusion: Intravenous acetaminophen is associated with a reduction in intraoperative opioids during transsphenoidal pituitary surgery.
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http://dx.doi.org/10.4103/joacp.JOACP_276_17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6360881PMC
February 2019

Pazopanib in patients with von Hippel-Lindau disease: a single-arm, single-centre, phase 2 trial.

Lancet Oncol 2018 10 17;19(10):1351-1359. Epub 2018 Sep 17.

Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Background: No approved systemic therapy exists for von Hippel-Lindau disease, an autosomal dominant disorder with pleiotropic organ manifestations that include clear cell renal cell carcinomas; retinal, cerebellar, and spinal haemangioblastomas; pheochromocytomas; pancreatic serous cystadenomas; and pancreatic neuroendocrine tumours. We aimed to assess the activity and safety of pazopanib in patients with von Hippel-Lindau disease.

Methods: In this non-randomised, single-centre, open-label, phase 2 trial, adult patients with clinical manifestations of von Hippel-Lindau disease were recruited from the University of Texas MD Anderson Cancer Center (Houston, TX, USA) and were treated with pazopanib (800 mg orally daily) for 24 weeks, with an option to continue treatment if desired by the patient and treating physician. Primary endpoints were the proportion of patients who achieved an objective response and safety in the per-protocol population. The objective response was measured for each patient and each lesion type. Radiographic assessments were done at baseline and every 12 weeks throughout the study. Activity and safety were assessed with continuous monitoring and a Bayesian design. This study is registered with ClinicalTrials.gov, number NCT01436227, and is closed to accrual.

Findings: Between Jan 18, 2012, and Aug 10, 2016, we screened 37 patients with genetically confirmed or clinical features consistent with von Hippel-Lindau disease, of whom 31 eligible patients were treated with pazopanib. The proportion of patients who achieved an objective response was 42% (13 of 31 patients). By lesion sites responses were observed in 31 (52%) of 59 renal cell carcinomas, nine (53%) of 17 pancreatic lesions, and two (4%) of 49 CNS haemangioblastomas. Seven (23%) of 31 patients chose to stay on the treatment after 24 weeks. Four (13%) of 31 patients withdrew from the study because of grade 3 or 4 transaminitis, and three (10%) discontinued study treatment because of treatment intolerance with multiple intercurrent grade 1-2 toxicities. Treatment-related serious adverse events included one case each of appendicitis and gastritis and one patient had a fatal CNS bleed.

Interpretation: Pazopanib was associated with encouraging preliminary activity in von Hippel-Lindau disease, with a side-effect profile consistent with that seen in previous trials. Pazopanib could be considered as a treatment choice for patients with von Hippel-Lindau disease and growing lesions, or to reduce the size of unresectable lesions in these patients. The safety and activity of pazopanib in this setting warrants further investigation.

Funding: Novartis Inc and NIH National Cancer Institute core grant.
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http://dx.doi.org/10.1016/S1470-2045(18)30487-XDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6338228PMC
October 2018

Pilot study of dovitinib in patients with von Hippel-Lindau disease.

Oncotarget 2018 May 4;9(34):23390-23395. Epub 2018 May 4.

Department of Genitourinary Medical Oncology, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Von Hippel-Lindau (VHL) disease is an autosomal dominant disease occurring in 1 in 35,000 births and leads to an increased risk of a phenotypically diverse array of tumor types including, but not limited to, clear cell renal cell carcinoma (ccRCC) and hemangioblastomas (HBs). Previous studies of patients with VHL disease treated with the tyrosine kinase inhibitor (TKI) sunitinib did not show clinical response in HBs. Interestingly, VHL-related HBs displayed increased fibroblast growth factor receptor 3 (FGFR3) protein expression when compared to VHL-related ccRCCs. Therefore, in this pilot study, we assessed the safety and efficacy profile of TKI 258 (dovitinib), a multi-tyrosine kinase inhibitor of VEGF receptor and fibroblast growth factor (FGF), in patients with VHL disease who had measureable HBs. The trial was stopped after six patients enrolled after the toxicity stopping rule was triggered. With regards to safety, 6/6 subjects had at least one adverse event (AE). Best response in 6/6 subjects was stable disease (SD) in HBs. While the negative safety and efficacy results of this pilot study do not favor the use of dovitinib for the treatment of asymptomatic HBs in VHL disease patients, further investigation into alternative scheduling and other FGFR inhibitors for the treatment of HBs in VHL disease patients is warranted given the promising pre-clinical and molecular data.
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http://dx.doi.org/10.18632/oncotarget.25171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5955100PMC
May 2018

Low-Dose and Standard Overnight and Low Dose-Two Day Dexamethasone Suppression Tests in Patients with Mild and/or Episodic Hypercortisolism.

Horm Metab Res 2018 Jun 2;50(6):453-461. Epub 2018 May 2.

Division of Endocrinology, Metabolism, and Molecular Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, CA, USA.

We previously reported on the lack of utility of the 1 mg overnight dexamethasone (DEX) test in mild and/or periodic Cushing's syndrome, as most patients with the condition suppressed to 1 mg DEX. It is possible that a lower dose of DEX as part of an overnight DEX test might be able to distinguish between mild and/or periodic Cushing's syndrome and those without the condition. The objective of the current study is to determine the sensitivity and specificity of a 0.25 mg overnight DEX suppression test, the standard 1 mg overnight DEX suppression test, and the two-day low-dose (Liddle test) DEX suppression test with and without correction for DEX levels in patients evaluated for mild and/or periodic Cushing's syndrome. Thirty patients determined to have Cushing's syndrome by biochemical testing and 14 patients determined not to have the condition had the 0.25 mg and standard 1 mg overnight DEX suppression test and the two-day low-dose DEX suppression tests. Our results show that morning serum cortisol and cortisol/DEX ratios following an overnight dexamethasone suppression test were similar in patients with Cushing's syndrome and those not having Cushing's syndrome. However, a morning cortisol value above 7.6 μg/dl following a dose of DEX of 0.25 mg was found in 12 patients with Cushing's syndrome and none in those not having Cushing's syndrome, suggesting that a high cortisol value after this low dose of dexamethasone can indicate that further testing for Cushing's syndrome is warranted. Our data suggest that the traditional 1 mg overnight or the 2 mg/2 day DEX suppression testing should no longer be used as a screening test in patients who could have mild and/or periodic Cushing's syndrome, while the 0.25 mg dose of DEX may pick up some patients with mild Cushing's syndrome.
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http://dx.doi.org/10.1055/a-0603-3868DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6502760PMC
June 2018

Retrospective review of metastatic melanoma patients with leptomeningeal disease treated with intrathecal interleukin-2.

ESMO Open 2018 24;3(1):e000283. Epub 2018 Jan 24.

Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

Objectives: Metastatic melanoma patients with leptomeningeal disease (LMD) have an extremely poor prognosis, with a median survival measured in weeks, and few treatment options. Outcomes of a retrospective cohort of patients with LMD that were treated with intrathecal interleukin-2 (IT IL-2) were reviewed to assess the long-term efficacy of this therapy.

Methods: The records of metastatic melanoma patients with LMD who were treated with IT IL-2 from 2006 to 2014 in a Compassionate Investigational New Drug study were reviewed. IL-2 (1.2 mIU) was administered intrathecally via Ommaya reservoir up to five times per week in the inpatient setting for 4 weeks; patients with good tolerance and clinical benefit received maintenance IT IL-2 every 1-3 months thereafter.

Results: The cohort included 43 patients. The median age of the patients was 47 years (range 18-71), and 32 (74%) were male. 23 patients (53%) had positive cerebrospinal fluid (CSF) cytology and radiographic evidence of LMD, 8 (19%) had positive CSF cytology only, 9 (21%) had radiographic evidence only and 3 (7%) were diagnosed based on pathology review after craniotomy. The median overall survival (OS) from initiation of IT IL-2 was 7.8 months (range, 0.4-90.8 months), with 1-year, 2-year and 5-year OS rates of 36%, 26% and 13%. The presence of neurological symptoms (HR 2.1, P=0.03), positive baseline CSF cytology (HR 4.1, P=0.001) and concomitant use of targeted therapy (HR 3.0, P=0.02) was associated with shorter OS on univariate analysis. All patients developed symptoms due to increased intracranial pressure which was managed with supportive medications and/or CSF removal, and there were no treatment-related deaths.

Conclusion: These results demonstrate that despite their historically dismal prognosis a subset of metastatic melanoma patients with LMD treated with IT IL-2 can achieve long-term survival, but these data need to be verified in a prospective trial setting.
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http://dx.doi.org/10.1136/esmoopen-2017-000283DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5786950PMC
January 2018

Surgical Management of Gliomas in Eloquent Cortex.

Prog Neurol Surg 2018 14;30:159-172. Epub 2017 Dec 14.

Gliomas located in eloquent cortex impose a unique surgical obstacle. The oncological benefit of aggressive resection must be balanced with preservation of functional tissue and optimization of surgical outcome. Technical advances in preoperative functional imaging, refinement of intraoperative mapping, and conceptual understanding of cerebral plasticity have significantly improved the outcome of this patient population.
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http://dx.doi.org/10.1159/000464391DOI Listing
July 2018

Rationale for Aggressive Resection and General Surgical Principles for Intracranial Gliomas.

Prog Neurol Surg 2018 14;30:63-105. Epub 2017 Dec 14.

Given the infiltrative nature of gliomas, controversy has long persisted over the value of their aggressive surgical removal. Nevertheless, in recent decades, the balance of opinion in neurosurgical oncology has shifted from a more nihilistic view that led to many patients' receiving stereotactic biopsy or very limited debulking of lesions for tissue diagnosis only, to more extensive tumor resections which relieve mass effect, lower intracranial pressure, reduce accompanying brain edema, and attenuate dependence on steroids. Achieving a clinically significant cytoreduction makes adjuvant therapy more successful, and ultimately helps to preserve or improve neurological function. Moreover, increased extent of brain tumor removal results in prolongation of progression-free survival and overall survival of patients and improves their quality of life. The beneficial effect of high resection rate may be noted even in selected cases of recurrent neoplasms. However, optimizing an aggressive surgical strategy for intracranial gliomas requires specific skills, availability of advanced intraoperative technological modalities, and the presence of a highly qualified multidisciplinary team of medical professionals for pre-, intra-, and postoperative care of such patients.
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http://dx.doi.org/10.1159/000464369DOI Listing
July 2018

The surgical treatment of metastatic spine tumors within the intramedullary compartment.

J Neurosurg Spine 2018 01 10;28(1):79-87. Epub 2017 Nov 10.

OBJECTIVE Metastasis to the spinal cord is rare, and optimal management of this disease is unclear. The authors investigated this issue by analyzing the results of surgical treatment of spinal intramedullary metastasis (IM) at a major cancer center. METHODS The authors retrospectively reviewed the medical records of 13 patients who underwent surgery for IM. Patients had renal cell carcinoma (n = 4), breast carcinoma (n = 3), melanoma (n = 2), non-small cell lung cancer (n = 1), sarcoma (n = 1), adenoid cystic carcinoma (n = 1), and cervical cancer (n = 1). Cerebrospinal fluid was collected before surgery in 11 patients, and was negative for malignant cells, as was MRI of the neuraxis. Eleven patients presented with neurological function equivalent to Frankel Grade D. RESULTS Radiographic gross-total resection was achieved in 9 patients, and tumor eventually recurred locally in 3 of those 9 (33%). Leptomeningeal disease was diagnosed in 4 patients after surgery. In the immediate postoperative period, neurological function in 6 patients deteriorated to Frankel Grade C. At 2 months, only 2 patients remained at Grade C, 8 were at Grade D, and 1 had improved to Grade E. One patient developed postoperative hematoma resulting in Frankel Grade A. Radiotherapy was delivered in 8 patients postoperatively. The median survival after spine surgery was 6.5 months. Three patients are still living. CONCLUSIONS Surgery was performed as a last option to preserve neurological function in patients with IM. In most patients, neurological function returned during the immediate postoperative period and was preserved for the patients' remaining lifetime. The data suggest that surgery can be effective in preventing further decline in selected patients with progressive neurological deficit.
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http://dx.doi.org/10.3171/2017.5.SPINE161161DOI Listing
January 2018

Interbody distraction and vertebral body reconstruction with polymethylmethacrylate for the treatment of pathological fractures.

J Neurosurg Spine 2017 Dec 6;27(6):700-708. Epub 2017 Oct 6.

2Department of Neurological Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.

OBJECTIVE Treatment of epidural spinal cord compression (ESCC) caused by tumor includes surgical decompression and stabilization followed by postoperative radiation. In the case of severe axial loading impairment, anterior column reconstruction is indicated. The authors describe the use of interbody distraction to restore vertebral body height and correct kyphotic angulation prior to reconstruction with polymethylmethacrylate (PMMA), and report the long-term durability of such reconstruction. METHODS A single institution, prospective series of patients with ESCC undergoing single-stage decompression, anterior column reconstruction, and posterior instrumentation from 2013 to 2016 was retrospectively analyzed. Several demographic, perioperative, and radiographic measurements were collected. Descriptive statistics were compiled, in addition to postoperative changes in anterior height, posterior height, and kyphosis. Paired Student t-tests were performed for each variable. Overall survival was calculated using the techniques described by Kaplan and Meier. RESULTS Twenty-one patients underwent single-stage posterior decompression with interbody distraction and anterior column reconstruction using PMMA. The median age and Karnofsky Performance Scale score were 61 years and 70, respectively. Primary tumors included renal cell (n = 8), lung (n = 4), multiple myeloma (n = 2), prostate (n = 2), and other (n = 5). Eighteen patients underwent a single-level vertebral body reconstruction and 3 underwent multilevel transpedicular corpectomies. The median survival duration was 13.3 months. In the immediate postoperative setting, statistically significant improvement was noted in anterior body height (p = 0.0017, 95% confidence interval [CI] -4.15 to -1.11) and posterior body height (p = 0.0116, 95% CI -3.14 to -0.45) in all patients, and improved kyphosis was observed in those with oblique endplates (p = 0.0002, 95% CI 11.16-20.27). In the median follow-up duration of 13.9 months, the authors observed 3 cases of asymptomatic PMMA subsidence. One patient required reoperation in the form of extension of fusion. CONCLUSIONS In situ interbody distraction allows safe and durable reconstruction with PMMA, restores vertebral height, and corrects kyphotic deformities associated with severe pathological fractures caused by tumor. This is accomplished with minimal manipulation of the thecal sac and avoiding an extensive 360° surgical approach in patients who cannot tolerate extensive surgery.
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http://dx.doi.org/10.3171/2017.4.SPINE161182DOI Listing
December 2017

Neurosurgical management of brain metastases.

Clin Exp Metastasis 2017 10 30;34(6-7):377-389. Epub 2017 Sep 30.

Department of Neurosurgery, The University of Texas M.D. Anderson Cancer Center, 1400 Holcombe Blvd, Houston, TX, 77030, USA.

Brain metastases present a significant public health issue, affecting more than 100,000 patients per year in the U.S. and result in significant morbidity. Brain metastases can occur in a variety of clinical situations ranging from multiple brain metastases with uncontrolled systemic disease to a solitary metastasis in the setting of controlled systemic disease. Additionally, advances in genomics have broadened the opportunities for targeted treatment options and potentially more durable systemic responses. As such, the treatment of brain metastases is now more tailored and multimodal, involving systemic, radiation, and surgical therapies, often in combination. This review discusses the historical and current role of neurosurgical techniques in the treatment of brain metastases.
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http://dx.doi.org/10.1007/s10585-017-9860-zDOI Listing
October 2017

Clinicopathological variables of sporadic schwannomas of peripheral nerve in 291 patients and expression of biologically relevant markers.

J Neurosurg 2018 09 8;129(3):805-814. Epub 2017 Sep 8.

5Neurosurgery and.

OBJECTIVE While sporadic peripheral schwannomas (SPSs) are generally well treated with surgery, their biology is not well understood. Consequently, treatment options are limited. The aim of this study was to provide a comprehensive description of SPS. The authors describe clinicopathological features and treatment outcomes of patients harboring these tumors, and they assess expression of biomarkers using a clinically annotated tissue microarray. Together, these data give new insight into the biology and management of SPS. METHODS Patients presenting with a primary SPS between 1993 and 2011 (n = 291) were selected from an institutional registry to construct a clinical database. All patients underwent follow-up, and short- and long-term outcomes were assessed. Expression of relevant biomarkers was assessed using a new tissue microarray (n = 121). RESULTS SPSs were generally large (mean 5.5 cm) and frequently painful at presentation (55%). Most patients were treated with surgery (80%), the majority of whom experienced complete resolution (52%) or improvement (18%) of their symptoms. Tumors that were completely resected (85%) did not recur. Some patients experienced short-term (16%) and long-term (4%) complications postoperatively. Schwannomas expressed higher levels of platelet-derived growth factor receptor-β (2.1) than malignant peripheral nerve sheath tumors (MPNSTs) (1.5, p = 0.004) and neurofibromas (1.33, p = 0.007). Expression of human epidermal growth factor receptor-2 was greater in SPSs (0.91) than in MPNSTs (0.33, p = 0.002) and neurofibromas (0.33, p = 0.026). Epidermal growth factor receptor was expressed in far fewer SPS cells (10%) than in MPNSTs (58%, p < 0.0001) or neurofibromas (37%, p = 0.007). SPSs more frequently expressed cytoplasmic survivin (66% of tumor cells) than normal nerve (46% of cells), but SPS expressed nuclear survivin in fewer tumor cells than in MPNSTs (24% and 50%, respectively; p = 0.018). CONCLUSIONS Complete resection is curative for SPS. Left untreated, however, these tumors can cause significant morbidity, and not all patients are candidates for resection. SPSs express a pattern of biomarkers consistent with the dysregulation of the tumor suppressor merlin observed in neurofibromatosis Type 2-associated schwannomas, suggesting a shared etiology. This SPS pattern is distinct from that of other tumors of the peripheral nerve sheath.
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http://dx.doi.org/10.3171/2017.2.JNS153004DOI Listing
September 2018

HNF1B Loss Exacerbates the Development of Chromophobe Renal Cell Carcinomas.

Cancer Res 2017 10 14;77(19):5313-5326. Epub 2017 Aug 14.

Department of Bioinformatics and Computational Biology, University of Texas at MD Anderson Cancer Center, Houston, Texas.

Chromophobe renal cell carcinoma (ChRCC) is characterized by major changes in chromosomal copy number (CN). No model is available to precisely elucidate the molecular drivers of this tumor type. HNF1B is a master regulator of gene expression. Here, we report that the transcription factor HNF1B is downregulated in the majority of ChRCC and that the magnitude of loss is unique to ChRCC. We also observed a strong correlation between reduced expression and aneuploidy in ChRCC patients. In murine embryonic fibroblasts or ACHN cells, deficiency reduced expression of the spindle checkpoint proteins MAD2L1 and BUB1B, and the cell-cycle checkpoint proteins RB1 and p27. Furthermore, it altered the chromatin accessibility of , , and genes and triggered aneuploidy development. Analysis of The Cancer Genome Atlas database revealed mutations in 33% of ChRCC where expression was repressed. In clinical specimens, combining loss with mutation produced an association with poor patient prognosis. In cells, combining loss and mutation increased cell proliferation and aneuploidy. Our results show how loss leads to abnormal mitotic protein regulation and induction of aneuploidy. We propose that coordinate loss of and may enhance cellular survival and confer an aggressive phenotype in ChRCC. .
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http://dx.doi.org/10.1158/0008-5472.CAN-17-0986DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5626626PMC
October 2017

Post-operative stereotactic radiosurgery versus observation for completely resected brain metastases: a single-centre, randomised, controlled, phase 3 trial.

Lancet Oncol 2017 08 4;18(8):1040-1048. Epub 2017 Jul 4.

Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address:

Background: After brain metastasis resection, whole brain radiotherapy decreases local recurrence, but might cause cognitive decline. We did this study to determine if stereotactic radiosurgery (SRS) to the surgical cavity improved time to local recurrence compared with that for surgical resection alone.

Methods: In this randomised, controlled, phase 3 trial, we recruited patients at a single tertiary cancer centre in the USA. Eligible patients were older than 3 years, had a Karnofsky Performance Score of 70 or higher, were able to have an MRI scan, and had a complete resection of one to three brain metastases (with a maximum diameter of the resection cavity ≤4 cm). Patients were randomly assigned (1:1) with a block size of four to either SRS of the resection cavity (within 30 days of surgery) or observation. Patients were stratified by histology of the primary tumour, metastatic tumour size, and number of metastases. The primary endpoint was time to local recurrence in the resection cavity, assessed by blinded central review of brain MRI scans by the study neuroradiologist in the modified intention-to-treat population that analysed patients by randomised allocation but excluded patients found ineligible after randomisation. Participants and other members of the treatment team (excluding the neuroradiologist) were not masked to treatment allocation. The trial is registered with ClinicalTrials.gov, number NCT00950001, and is closed to new participants.

Findings: Between Aug 13, 2009, and Feb 16, 2016, 132 patients were randomly assigned to the observation group (n=68) or SRS group (n=64), with 128 patients available for analysis; four patients were ineligible (three from the SRS group and one from the observation group). Median follow-up was 11·1 months (IQR 4·8-20·4). 12-month freedom from local recurrence was 43% (95% CI 31-59) in the observation group and 72% (60-87) in the SRS group (hazard ratio 0·46 [95% CI 0·24-0·88]; p=0·015). There were no adverse events or treatment-related deaths in either group.

Interpretation: SRS of the surgical cavity in patients who have had complete resection of one, two, or three brain metastases significantly lowers local recurrence compared with that noted for observation alone. Thus, the use of SRS after brain metastasis resection could be an alternative to whole-brain radiotherapy.

Funding: National Institutes of Health.
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http://dx.doi.org/10.1016/S1470-2045(17)30414-XDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5560102PMC
August 2017

The surgical treatment of tumors of the fourth ventricle: a single-institution experience.

J Neurosurg 2018 02 14;128(2):339-351. Epub 2017 Apr 14.

OBJECTIVE Fourth ventricle tumors are rare, and surgical series are typically small, comprising a single pathology, or focused exclusively on pediatric populations. This study investigated surgical outcome and complications following fourth ventricle tumor resection in a diverse patient population. This is the largest cohort of fourth ventricle tumors described in the literature to date. METHODS This is an 18-year (1993-2010) retrospective review of 55 cases involving patients undergoing surgery for tumors of the fourth ventricle. Data included patient demographic characteristics, pathological and radiographic tumor characteristics, and surgical factors (approach, surgical adjuncts, extent of resection, etc.). The neurological and medical complications following resection were collected and outcomes at 30 days, 90 days, 6 months, and 1 year were reviewed to determine patient recovery. Patient, tumor, and surgical factors were analyzed to determine factors associated with the frequently encountered postoperative neurological complications. RESULTS There were no postoperative deaths. Gross-total resection was achieved in 75% of cases. Forty-five percent of patients experienced at least 1 major neurological complication, while 31% had minor complications only. New or worsening gait/focal motor disturbance (56%), speech/swallowing deficits (38%), and cranial nerve deficits (31%) were the most common neurological deficits in the immediate postoperative period. Of these, cranial nerve deficits were the least likely to resolve at follow-up. Multivariate analysis showed that patients undergoing a transvermian approach had a higher incidence of postoperative cranial nerve deficits, gait disturbance, and speech/swallowing deficits than those treated with a telovelar approach. The use of surgical adjuncts (intraoperative navigation, neurophysiological monitoring) did not significantly affect neurological outcome. Twenty-two percent of patients required postoperative CSF diversion following tumor resection. Patients who required intraoperative ventriculostomy, those undergoing a transvermian approach, and pediatric patients (< 18 years old) were all more likely to require postoperative CSF diversion. Twenty percent of patients suffered at least 1 medical complication following tumor resection. Most complications were respiratory, with the most common being postoperative respiratory failure (14%), followed by pneumonia (13%). CONCLUSIONS The occurrence of complications after fourth ventricle tumor surgery is not rare. Postoperative neurological sequelae were frequent, but a substantial number of patients had neurological improvement at long-term followup. Of the neurological complications analyzed, postoperative cranial nerve deficits were the least likely to completely resolve at follow-up. Of all the patient, tumor, and surgical variables included in the analysis, surgical approach had the most significant impact on neurological morbidity, with the telovelar approach being associated with less morbidity.
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http://dx.doi.org/10.3171/2016.11.JNS161167DOI Listing
February 2018

Leptomeningeal metastases presenting exclusively with ocular disturbance in 34 patients: A tertiary care cancer hospital experience.

J Clin Neurosci 2017 May 16;39:151-154. Epub 2017 Feb 16.

Department of Neurosurgery, Baylor College of Medicine, Houston, TX, USA; Department of Neurosurgery, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA. Electronic address:

Leptomeningeal disease (LMD) represents disseminated intracranial metastatic disease that requires early detection and initiation of therapy. Patients with LMD typically present with a variety of neurologic problems, including ocular disturbances. However, little is reported on LMD presenting exclusively with ocular-related disturbances in the absence of any other central nervous system (CNS) dysfunction. Our goal was to describe the workup for ocular disturbances in the setting of known cancer diagnosis. Retrospective case study utilizing prospectively collected database at a tertiary cancer care center for all patients with diagnosis of LMD between 2001 and 2009. Main outcome was descriptive analysis of ocular findings by primary or admitting service with or without formal ophthalmology exam in workup for LMD. 34 patients demonstrated ocular disturbances without any other CNS manifestations. Our findings demonstrate that 71% of ocular disturbances were detected by the primary admitting services. Formal consultation with ophthalmology resulted in the detection of the remaining cases. The most common findings were cranial nerve deficits, papilledema, and optic disc or retinal infiltration by tumor. These findings supported a further work-up for CNS disease. Therefore, it is appropriate to refer cancer patients with visual complaints or findings on exam to ophthalmology to evaluate for evidence suggestive of LMD that may support a further work-up.
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http://dx.doi.org/10.1016/j.jocn.2017.01.024DOI Listing
May 2017

Metastatic Adenoid Cystic Carcinoma Mimicking Butterfly Glioblastoma: A Rare Presentation in the Splenium of the Corpus Callosum.

World Neurosurg 2016 Nov 10;95:621.e13-621.e19. Epub 2016 Aug 10.

Department of Neurosurgery, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA. Electronic address:

Background: Intracranial spread of an adenoid cystic carcinoma (ACC) of the parotid gland is rare, and metastatic ACC to the splenium of the corpus callosum mimicking butterfly glioblastoma (GBM) has not been reported previously. We report a rare case of metastasis to the splenium of the corpus callosum from ACC of the parotid gland.

Case Description: The tumor occupied the splenium and mimicked the presentation of a butterfly glioma. The patient had undergone parotidectomy 5 years before presentation with this intracranial lesion. On magnetic resonance imaging, the lesion was separate from the pineal gland and displaced the internal cerebral veins downward. Ventricular obstruction and increased cellularity were also suggested, and multiple fluid-filled cystic spaces were observed. The tumor was partially resected, because the extreme lateral boundary could not be visualized. Histological analysis with anti-c-kit antibody showed strong expression of the epithelial component; immunohistochemistry with anti-p63 antibody revealed nests of positive tumor cells, highlighting the myoepithelial component. The tumor also stained positive for anti-Myb antibody.

Conclusions: The treatment for this lesion is surgical debulking followed by radiation therapy; however, the overall prognosis remains grim because of limited chemotherapy options and a propensity for recurrence in both local and distant fashions. When a tumor with adenoid histological features and a "butterfly" phenotype grows in the corpus callosum in a patient with known parotid ACC, both metastasis and adenoid variant GBM should be considered. Careful clinical and radiological correlation is required to diagnose and treat this rare lesion.
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http://dx.doi.org/10.1016/j.wneu.2016.07.111DOI Listing
November 2016

Radiotherapy with concurrent temozolomide for the management of extraneural metastases in pituitary carcinoma.

Pituitary 2016 Aug;19(4):415-21

Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, 1400 Holcombe Blvd, Room FC7.3000, Unit 431, Houston, TX, 77030, USA.

Background: Pituitary carcinomas (PC) are uncommon neuroendocrine tumors, accounting for 0.1 % of all pituitary tumors. The diagnosis of PC is based on the presence of metastases from a pituitary adenoma, and not by local invasion or pathological features alone. PC is typically resistant to therapy, with a median overall survival of only 31 months. There is no standard treatment for PC, but maximal safe resection and radiation are performed when possible. Encouraging preliminary data on the use of temozolomide (TMZ)-based therapy has been previously reported.

Methods: We report the response to therapy and safety of radiation with concurrent temozolomide (RT/TMZ) in 2 adult patients with heavily pretreated PC and extraneural metastases.

Results: Both patients had prior history of pituitary macroadenoma. At the time of diagnosis of PC, Ki-67 % was 24.2 and 10 %, with positive p53 staining in one case. Metastatic sites included lymph nodes, liver and bone. Case-1 received RT/TMZ to the tumor bed in the skull base and to the metastases in the cervical lymph nodes. Case-2 received RT/TMZ to recurrent tumor involving portacaval lymph nodes. Both patients achieved excellent long-term control of the sites of treated extraneural metastases, with no significant acute or delayed toxicity.

Conclusions: RT/TMZ was safely delivered and might provide sustained control of extraneural metastases in PC. Although this retrospective report has limitations, RT/TMZ can be considered as a therapeutic option for the management of extraneural metastases in PC.
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http://dx.doi.org/10.1007/s11102-016-0721-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5215904PMC
August 2016

Patterns of recurrence and survival in sporadic, neurofibromatosis Type 1-associated, and radiation-associated malignant peripheral nerve sheath tumors.

J Neurosurg 2017 Jan 1;126(1):319-329. Epub 2016 Apr 1.

Departments of 1 Surgical Oncology.

OBJECTIVE Malignant peripheral nerve sheath tumors (MPNSTs) are an aggressive group of soft tissue sarcomas that can arise sporadically, in the context of neurofibromatosis Type 1 (NF1) or at a site of prior irradiation. Large series profiling the features and outcomes of sporadic, NF1-associated, and radiation-associated MPNSTs are limited. The goal of this study was to elucidate differences between MPNST etiologies in a large single-institution retrospective study. METHODS Patients (n = 317) were identified through the tumor registry of The University of Texas MD Anderson Cancer Center. Clinicopathological features were retrospectively collected. Features were compared among MPNST subtypes for patients who had sufficient clinical history (n = 289), and clinicopathological features were used to identify adverse predictors of recurrence and survival outcomes. RESULTS Five-year local recurrence-free survival (LRFS), distant recurrence-free survival (DRFS), and disease-specific survival (DSS) estimates were 56.6%, 49.6%, and 53.6%, respectively, for the high-grade MPNST cohort. Five-year DSS was lower in NF1-associated and radiation-associated MPNST than in sporadic MPNST (52%, 47%, and 67%, respectively, p = 0.140). Patients with radiation-associated MPNST had worse 5-year LRFS than those with the sporadic and NF1-associated subtypes (RT-associated vs sporadic, p = 0.010; RT-associated vs NF1-associated, p = 0.232). Truncally located tumors, positive surgical margins, local recurrence, and metastasis were predictors of adverse DSS in multivariate analysis. CONCLUSIONS Radiation-associated MPNSTs are associated with poorer local recurrence-free and disease-specific survival than sporadic and NF1-associated tumors. NF1-associated MPNSTs may have worse survival outcomes owing to large tumor size, compromising truncal location, and lower rate of negative resection margins compared with sporadic tumors.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5045773PMC
http://dx.doi.org/10.3171/2015.12.JNS152443DOI Listing
January 2017

Key considerations in the treatment of von Hippel-Lindau disease.

Future Oncol 2016 Aug 29;12(15):1755-8. Epub 2016 Mar 29.

Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

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http://dx.doi.org/10.2217/fon-2016-0028DOI Listing
August 2016