E Antonio Chiocca

Dana-Farber Cancer Institute, Boston, Massachusetts, United States

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Publications (301)1614.11 Total impact

  • A. Bronisz · M. Mineo · R. Ferrer-Luna · E. A. Chiocca · J. Godlewski ·

    Neuro-Oncology 11/2015; 17(suppl 5):v69-v69. DOI:10.1093/neuonc/nov211.01 · 5.56 Impact Factor
  • E Antonio Chiocca · Hiroshi Nakashima · Tran Nguyen ·

    11/2015; DOI:10.2147/OV.S66081
  • D. Ogawa · S. Hu · M. Okada · K. Miyake · T. Tamiya · E. A. Chiocca · J. Godlewski ·

    Neuro-Oncology 11/2015; 17(suppl 5):v126-v126. DOI:10.1093/neuonc/nov219.11 · 5.56 Impact Factor
  • A. Rooj · P. Peruzzi · A. Bronisz · E. A. Chiocca · J. Godlewski ·

    Neuro-Oncology 11/2015; 17(suppl 5):v210-v210. DOI:10.1093/neuonc/nov234.09 · 5.56 Impact Factor
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    ABSTRACT: Metastatic tumors are the most common cranial neoplasms in adults. Skull metastases from rare primary tumors, such as cholangiocarcinoma or pancreatic neuroendocrine tumor, are extremely uncommon and rarely reported. Given the scarcity and variation of these rare skull metastases, treatments and outcomes of such patients are of interest to treating surgeons.The authors describe the treatment algorithm, course, and outcomes of 2 patients with rare gastrointestinal skull metastases. The first patient had intrahepatic cholangiocarcinoma metastatic to the skull, while the second patient developed a solitary skull metastasis secondary to a pancreatic neuroendocrine tumor. As part of this report, the authors include a literature review of rare skull metastases as well as the treatment of these 2 patients.Both the patients ultimately underwent successful resection of the tumor for relief of their clinical symptoms. Wide resections in both patients necessitated reconstruction using a free latissimus dorsi muscle flap in both the patients. Preoperative embolization of the hypervascular cholangiocarcinoma skull metastasis was performed prior to resection in the first patient. To date, there have been only 4 such reports of skull metastases from intrahepatic cholangiocarcinoma and limited reported cases of isolated skull metastases from a pancreatic neuroendocrine tumor.In patients with large or numerous skull metastasis from rare primary tumors, surgical resection should be considered for symptomatic improvement. In cases of hypervascular lesions, preoperative embolization can be considered to decrease the intraoperative bleeding. Free tissue transfers using myocutaneous flaps such as latissimus dorsi help in obliterating dead space, and creating a healthy soft tissue envelope to withstand postoperative radiation treatment. In addition, a chimeric flap can be designed to include additional muscle or soft tissue to obliterate and exclude the sinus cavities.
    The Journal of craniofacial surgery 10/2015; DOI:10.1097/SCS.0000000000002218 · 0.68 Impact Factor
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    ABSTRACT: Oncolytic viral (OV) therapy, which uses genetically engineered tumor-targeting viruses, is being increasingly used in cancer clinical trials due to the direct cytolytic effects of this treatment that appear to provoke a robust immune response against the tumor. As OVs enter tumor cells, intrinsic host defenses have the potential to hinder viral replication and spread within the tumor mass. In this report, we show that histone deacetylase 6 (HDAC6) in tumor cells appears to alter the trafficking of post-entry OVs from the nucleus toward lysosomes. In glioma cell lines and glioma-stem-like cells, HDAC6 inhibition (HDAC6i) by either pharmacologic or genetic means substantially increased replication of oncolytic herpes simplex virus type 1 (oHSV). Moreover, HDAC6i increased shuttling of post-entry oHSV to the nucleus. In addition, electron microscopic analysis revealed that post-entry oHSVs are preferentially taken up into glioma cells through the endosomal pathway rather than via fusion at the cell surface. Together, these findings illustrate a mechanism of glioma cell defense against an incoming infection by oHSV and identify possible approaches to enhance oHSV replication and subsequent lysis of tumor cells.
    Journal of Clinical Investigation 10/2015; 125(11). DOI:10.1172/JCI80713 · 13.22 Impact Factor
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    ABSTRACT: Despite the challenge of implementing oncolytic viral therapy into mainstream clinical use, the obstacles of early clinical trials have outlined numerous areas requiring additional investigation. In particular, the role of innate and adaptive immunity has received significant attention in this context. It is increasingly clear that a one-sided approach of either immune suppression or robust immune cell activation is not the answer for clinical success. Rather, recent studies are increasingly demonstrating the delicate balance between both anti-viral immune suppression and immune mediated tumor killing. In this review we focus on aspects of innate immune cell activation following oncolytic viral infection and how this response has the potential of bridging to the broader goal of viral mediated immunotherapy. Copyright © 2015. Published by Elsevier B.V.
    Current Opinion in Virology 08/2015; 13. DOI:10.1016/j.coviro.2015.03.015 · 6.06 Impact Factor
  • Mohammad Abolfotoh · Peleg M Horowitz · E Antonio Chiocca ·

    Neurosurgery 08/2015; DOI:10.1227/NEU.0000000000000966 · 3.62 Impact Factor
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    ABSTRACT: We report the indications and outcomes of awake right hemispheric brain surgery, as well as a rare patient with crossed aphasia. Awake craniotomies are often performed to protect eloquent cortex. We reviewed the medical records for 35 of 96 patients, in detail, who had awake right hemisphere brain operations. Intraoperative cortical mapping of motor and/or language function was performed in 29 of the 35 patients. A preoperative speech impairment and left hand dominance were the main indicators for awake right-sided craniotomies in patients with right hemisphere lesions. Four patients with lesion proximity to eloquent areas underwent awake craniotomies without cortical mapping. In addition, one patient had a broncho-pulmonary fistula, and another had a recent major cardiac procedure that precluded awake surgery. An eloquent cortex representation was identified in 14 patients (48.3%). Postoperatively, seven of 17 patients (41.1%) who presented with weakness, experienced improvements in their motor functions, 11 of 16 (68.7%) with seizures became seizure-free, and seven of nine (77.7%) with moderate to severe headaches and one of two with a visual field deficit improved significantly. There were also improvements in speech and language functions in all patients who presented with speech difficulties. A right sided awake craniotomy is an excellent option for left handed patients, or those with right sided cortical lesions that result in preoperative speech impairments. When combined with intraoperative cortical mapping, both speech and motor function can be well preserved. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Journal of Clinical Neuroscience 08/2015; DOI:10.1016/j.jocn.2015.06.009 · 1.38 Impact Factor

  • Cancer Research 08/2015; 75(15 Supplement):299-299. DOI:10.1158/1538-7445.AM2015-299 · 9.33 Impact Factor
  • Sean E Lawler · E Antonio Chiocca ·

    Journal of Clinical Oncology 07/2015; 33(25). DOI:10.1200/JCO.2015.62.5244 · 18.43 Impact Factor
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    Agnieszka Bronisz · E Antonio Chiocca · Jakub Godlewski ·

    Oncotarget 07/2015; 6(20):17851-2. DOI:10.18632/oncotarget.4606 · 6.36 Impact Factor
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    ABSTRACT: Glioblastoma (GB) remains the most aggressive primary brain malignancy. Adoptive transfer of chimeric antigen receptor (CAR)-modified immune cells has emerged as a promising anti-cancer approach, yet the potential utility of CAR-engineered natural killer (NK) cells to treat GB has not been explored. Tumors from approximately 50% of GB patients express wild-type EGFR (wtEGFR) and in fewer cases express both wtEGFR and the mutant form EGFRvIII; however, previously reported CAR T cell studies only focus on targeting EGFRvIII. Here we explore whether both wtEGFR and EGFRvIII can be effectively targeted by CAR-redirected NK cells to treat GB. We transduced human NK cell lines NK-92 and NKL, and primary NK cells with a lentiviral construct harboring a second generation CAR targeting both wtEGFR and EGFRvIII and evaluated the anti-GB efficacy of EGFR-CAR-modified NK cells. EGFR-CAR-engineered NK cells displayed enhanced cytolytic capability and IFN-γ production when co-cultured with GB cells or patient-derived GB stem cells in an EGFR-dependent manner. In two orthotopic GB xenograft mouse models, intracranial administration of NK-92-EGFR-CAR cells resulted in efficient suppression of tumor growth and significantly prolonged the tumor-bearing mice survival. These findings support intracranial administration of NK-92-EGFR-CAR cells represents a promising clinical strategy to treat GB.
    Scientific Reports 07/2015; 5:11483. DOI:10.1038/srep11483 · 5.58 Impact Factor
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    ABSTRACT: Despite a high symptom burden, little is known about the incidence or predictors of hospitalization among glioblastoma patients, including risks during chemoradiation (CRT). We studied 196 consecutive newly diagnosed glioblastoma patients treated at our institution from 2006-2010. Toxicity data were reviewed during and after the CRT phase, defined as the period between diagnosis and 6 weeks after radiotherapy completion. Logistic regression and proportional hazards modeling identified predictors of hospitalization and overall survival (OS). Median age was 59 years (range, 23-90) and 83 % had Karnofsky performance status (KPS) score ≥ 70. Twenty-six percent of patients underwent gross total resection, 77 % received ≥ 59.4 Gy of radiotherapy, and 89 % received concurrent temozolomide. Median OS was 15.6 months (IQR, 8.5-26.8 months). Forty-three percent of patients were hospitalized during the CRT phase; OS was 10.7 vs. 17.8 months for patients who were vs. were not hospitalized, respectively (P P = .034) and KPS (OR, 0.95; 95 % CI, 0.93-0.97; P Hospitalization during the CRT phase was associated with decreased OS (adjusted hazard ratio, 1.47; 95 % CI, 1.01-2.13; P = .043), after adjustment for known prognostic factors. Hospitalization during the CRT phase is common among glioblastoma patients in the temozolomide era and is associated with shorter overall survival.
    Journal of Neuro-Oncology 06/2015; 124(1). DOI:10.1007/s11060-015-1820-3 · 3.07 Impact Factor
  • David A Reardon · Keith L Ligon · E Antonio Chiocca · Patrick Y Wen ·
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    ABSTRACT: Over the past few years, understanding the genetic abnormalities associated with glioblastoma, the most common malignant primary tumor of the central nervous system, has increased dramatically. Mutation types and frequencies have been comprehensively assessed, glioblastoma subclasses have been defined based on gene expression and methylation analyses, and novel mutations implicated in gliomagenesis have been identified. Nonetheless, a critical disconnect exists between achieved scientific advances and failure to improve patient outcome. Currently, standard therapy incorporating surgery, cranial irradiation, and temozolomide chemotherapy is uniformly applied for all patients. With this approach, median survival remains unacceptably poor including fewer than 10% of patients surviving 5 years after diagnosis. Salvage therapies are ineffective with PFS-6 rates under 10% for non-bevacizumab regimens and 40% for bevacizumab. Furthermore, all patients ultimately progress on bevacizumab, and then typically die from rapidly progressive tumor. Innovative treatment strategies directed to distinct patient subsets defined by specific genetic and gene expression analyses represent an attractive therapeutic paradigm shift for this highly challenging complex tumor, offering promise to ultimately improve outcome.
    Discovery medicine 06/2015; 19(107):471-7. · 3.63 Impact Factor
  • Agnieszka Bronisz · E Antonio Chiocca ·

    Nature medicine 05/2015; 21(5):426-7. DOI:10.1038/nm.3857 · 27.36 Impact Factor
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    ABSTRACT: We present a 59-year-old woman who noted an enlarging lump on her forehead 6months after a left frontotemporal craniotomy for tumor resection and chemoradiation of her primary glioblastoma multiforme (GBM). GBM is a highly aggressive intracranial neoplasm associated with the shortest survival time of any primary central nervous system malignancy. Extracranial metastasis is rare, especially without previous surgical disruption of the dura and calvarium, which has been postulated to cause seeding of the extracranial space with tumor cells. This patient's MRI revealed tumor recurrence for which she underwent repeat resection. Histopathology confirmed GBM with unmethylated O-6-methylguanine-DNA methyltransferase and wildtype isocitrate dehydrogenase 1 status, as well as tumor invasion through the bone and subdermal space. The genetic and molecular factors that predict extracranial invasion remain unclear and require further investigation. Emerging data on circulating tumor cells in GBM patients indicate that extraaxial metastasis may be part of the disease course in some, particularly in long term survivors. Furthermore, the proximity of calvarial and scalp lesions to previous surgical sites and the time course in which they emerge after surgery suggests that iatrogenic seeding may also play a role in metastasis. With heightened awareness of the phenomenon, surgical strategies such as watertight approximation of the dura, bone flap replacement, or changing surgical instruments once the intradural component is complete may prove useful to prevent seeding. Prophylactic craniospinal irradiation may also be an appropriate tool in patients at high risk for metastasis, although this population is difficult to identify. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Journal of Clinical Neuroscience 05/2015; 22(9). DOI:10.1016/j.jocn.2015.03.018 · 1.38 Impact Factor
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    ABSTRACT: In aggressive, rapidly growing solid tumors such as glioblastoma multiforme (GBM), cancer cells face frequent dynamic changes in their microenvironment, including the availability of glucose and other nutrients. These challenges require that tumor cells have the ability to adapt in order to survive periods of nutrient/energy starvation. We have identified a reciprocal negative feedback loop mechanism in which the levels of microRNA-451 (miR-451) are negatively regulated through the phosphorylation and inactivation of its direct transcriptional activator OCT1 by 5' AMP-activated protein kinase (AMPK), which is activated by glucose depletion-induced metabolic stress. Conversely, in a glucose-rich environment, unrestrained expression of miR-451 suppresses AMPK pathway activity. These findings uncover miR-451 as a major effector of glucose-regulated AMPK signaling, allowing tumor cell adaptation to variations in nutrient availability in the tumor microenvironment. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
    Cell Reports 04/2015; 11(6). DOI:10.1016/j.celrep.2015.04.016 · 8.36 Impact Factor
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    ABSTRACT: Older patients with newly diagnosed glioblastoma have poor outcomes, and optimal treatment is controversial. Hypofractionated radiation therapy (HRT) is frequently used but has not been compared to patients receiving standard fractionated radiation therapy (SRT) and temozolomide (TMZ). We conducted a retrospective analysis of patients ≥65 years of age who received radiation for the treatment of newly diagnosed glioblastoma from 1994 to 2013. The distribution of clinical covariates across various radiation regimens was analyzed for possible selection bias. Survival was calculated using the Kaplan-Meier method. Comparison of hypofractionated radiation (typically, 40 Gy/15 fractions) versus standard fractionation (typically, 60 Gy/30 fractions) in the setting of temozolomide was conducted using Cox regression and propensity score analysis. Patients received SRT + TMZ (n=57), SRT (n=35), HRT + TMZ (n=34), or HRT (n=9). Patients receiving HRT were significantly older (median: 79 vs 69 years of age; P<.001) and had worse baseline performance status (P<.001) than those receiving SRT. On multivariate analysis, older age (adjusted hazard ratio [AHR]: 1.06; 95% confidence interval [CI]: 1.01-1.10, P=.01), lower Karnofsky performance status (AHR: 1.02; 95% CI: 1.01-1.03; P=.01), multifocal disease (AHR: 2.11; 95% CI: 1.23-3.61, P=.007), and radiation alone (vs SRT + TMZ; SRT: AHR: 1.72; 95% CI: 1.06-2.79; P=.03; HRT: AHR: 3.92; 95% CI: 1.44-10.60, P=.007) were associated with decreased overall survival. After propensity score adjustment, patients receiving HRT with TMZ had similar overall survival compared with those receiving SRT with TMZ (AHR: 1.10, 95% CI: 0.50-2.4, P=.82). With no randomized data demonstrating equivalence between HRT and SRT in the setting of TMZ for glioblastoma, significant selection bias exists in the implementation of HRT. Controlling for this bias, we observed similar overall survival for HRT and SRT with concurrent TMZ among elderly patients, suggesting the need for a randomized trial to compare these regimens directly. Copyright © 2015 Elsevier Inc. All rights reserved.
    International journal of radiation oncology, biology, physics 04/2015; 92(2). DOI:10.1016/j.ijrobp.2015.01.017 · 4.26 Impact Factor
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    Richard Lee Price · Ennio Antonio Chiocca ·
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    ABSTRACT: The hypothesis that cytomegalovirus (CMV) modulates cancer is evolving. Originally discovered in glioblastoma in 2002, the number of cancers, where intratumoral CMV antigen is detected, has increased in recent years suggesting that CMV actively affects the pathobiology of certain tumors. These findings are controversial as several groups have also reported inability to replicate these results. Regardless, several clinical trials for glioblastoma are underway or have been completed that target intratumoral CMV with anti-viral drugs or immunotherapy. Therefore, a better understanding of the possible pathobiology of CMV in cancer needs to be ascertained. We have developed genetic, syngeneic, and orthotopic malignant glioma mouse models to study the role of CMV in cancer development and progression. These models recapitulate for the most part intratumoral CMV expression as seen in human tumors. Additionally, we discovered that CMV infection in Trp53(-/+) mice promotes pleomorphic rhabdomyosarcomas. These mouse models are not only a vehicle for studying pathobiology of the viral-tumor interaction but also a platform for developing and testing cancer therapeutics.
    Frontiers in Oncology 03/2015; 5:61. DOI:10.3389/fonc.2015.00061

Publication Stats

8k Citations
1,614.11 Total Impact Points


  • 2013-2015
    • Dana-Farber Cancer Institute
      Boston, Massachusetts, United States
  • 2012-2015
    • Brigham and Women's Hospital
      • Department of Neurosurgery
      Boston, Massachusetts, United States
    • Northwestern University
      • Department of Neurological Surgery
      Evanston, Illinois, United States
  • 1992-2015
    • Harvard Medical School
      • • Department of Radiology
      • • Department of Surgery
      • • Department of Medicine
      Boston, Massachusetts, United States
  • 2011-2014
    • Harvard University
      Cambridge, Massachusetts, United States
  • 2004-2014
    • Okayama University
      • Department of Neurological Surgery
      Okayama, Okayama, Japan
    • The Ohio State University
      • Department of Neurological Surgery
      Columbus, Ohio, United States
  • 2007
    • Comprehensive Cancer Centers of Nevada
      Las Vegas, Nevada, United States
  • 1990-2007
    • Massachusetts General Hospital
      • • Molecular Neurobiology Laboratory
      • • Department of Neurosurgery
      • • Department of Neurology
      Boston, Massachusetts, United States
  • 2005
    • Columbus State University
      Columbus, Georgia, United States
    • St. Jude Children's Research Hospital
      Memphis, Tennessee, United States
  • 2003
    • Partners HealthCare
      Boston, Massachusetts, United States