Ian F. Pollack, MD

A. Leland Albright Professor of Neurological Surgery
Vice Chairman of Academic Affairs
Chief, Pediatric Neurosurgery
Co-director, Neurosurgical Oncology


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Contact

412-692-5881

Biography

Ian Pollack, MD, is co-director of the Brain Tumor Program at the University of Pittsburgh Cancer Institute, chief of Pediatric Neurosurgery at Children’s Hospital of Pittsburgh, and A. leland Albright Professor of Neurosurgery at the University of Pittsburgh School of Medicine.

Prior to joining the faculty of the Department of Neurological Surgery at the University of Pittsburgh in 1992, he was awarded the 1991 Van Wagenen Traveling Fellowship, which afforded him a year of subspecialty training in the Department of Neurosurgery at the Hospital for Sick Children in Toronto, the Neuro-Oncology Laboratory of the University of Lausanne in Switzerland, and the Laboratory of Tumor Biology of the University of Uppsala in Sweden.

Dr. Pollack graduated magna cum laude from Emory University in 1980, where he earned a BS degree in chemistry. He received his medical degree from the Johns Hopkins University School of Medicine in 1984, then completed a surgical internship and neurosurgical residency at the University of Pittsburgh School of Medicine. He also was a research fellow in neuropathology and neurobiology during some of that time.

Pollack has published more than 250 papers in refereed journals, numerous book chapters and invited papers, and has edited two books on childhood brain tumors. He is co-editor of the recently published book Principles and Practice of Pediatric Neurosurgery and an accompanying atlas Operative Techniques In Pediatric Neurosurgery. He is currently a principal investigator on numerous NIH grants focusing on novel therapies for brain tumors and evaluating molecular markers of tumor prognosis. Dr. Pollack was named vice chairman of academic affairs for the department in July of 2008. He has co-chaired the National Cancer Institute Brain Malignancy Steering Committee since 2010.

Dr. Pollack's publications can be reviewed through the National Library of Medicine's publication database.

Board Certifications

American Board of Neurological Surgery
American Board of Pediatric Neurosurgery

Hospital Privileges

Children’s Hospital of Pittsburgh of UPMC
Magee-Womens Hospital of UPMC
UPMC Presbyterian

Professional Organization Membership

Alpha Omega Alpha
American Academy of Neurological Surgery
American Association for the Advancement of Science
American Association for Cancer Research
American Association of Neurological Surgeons (AANS)
American College of Surgeons
Association of American Physicians
Joint Section on Tumors (AANS/CNS)
American Society of Pediatric Neurosurgeons
American Society for Clinical Investigation
Children’s Oncology Group
Congress of Neurological Surgeons (CNS)
Johns Hopkins Medical and Surgical Society
Pennsylvania Neurosurgical Society
Phi Beta Kappa
Society of Neurological Surgeons
Society for Neuro-Oncology
Society of Surgical Oncology

Media Appearances

Glioma: Pilot Trial Shows Peptide Vaccine Active in Pediatric Patients
May 25, 2012
Oncology Times

First-of-its-kind Study of Peptide Vaccine by Pittsburgh Researchers Shows Evidence of Immunological Response in Children with Gliomas
April 4, 2012
HealthCanal.com

Study Suggests Vaccine May Help Kids With Brain Cancer
April 3, 2012
U.S. News and World Report Health Day

Study Suggests Vaccine May Help Kids With Brain Cancer
April 3, 2012
Health.com

Study Suggests Vaccine May Help Kids With Brain Cancer
April 3, 2012
MSN Health

Peptide vaccine shows evidence of immunological, clinical activity in children with gliomas
April 3, 2012
MedicalExpress.com

Brain Tumor Vaccine for Children
April 2, 2012
WTAJ-TV (Johnstown)

Teen Has New Lease On Life After Brain Tumor Removal 
July 22, 2009
WTAE TV-4 (Pittsburgh) Evening News

Study finds clue to deadly childhood brain cancers
February 7, 2002
Pittsburgh Post-Gazette

Research Activities

1) Molecular Markers of Prognosis in Gliomas

Malignant astrocytomas are among the most common and deadly brain tumors of childhood. Most affected children die within several years of diagnosis, despite current treatments; however, 20 to 30% respond favorably to therapy and are cured. The basis for these diverse outcomes has been enigmatic, even taking into account clinical and histological factors. In preliminary studies with an institutional cohort of pediatric gliomas, we observed that molecular markers could supplement histological data to refine prognostic assessments. Based on these findings, we began a more extensive study of the cohort of Children’s Cancer Group study CCG-945, the largest group of pediatric high-grade gliomas accrued to date, and subsequently the Children’s Oncology Group ACNS0126 study. The large size of these cohorts and the consistent treatment approaches used, coupled with the availability of central neuropathology review and comprehensive clinical data, provided a unique opportunity to address issues of molecular etiology and prognostic factors. Our studies demonstrated a striking association between outcome and several molecular features, including MGMT expression status, independent of clinical or histological factors; identified significant differences between molecular features of childhood and adult gliomas; and generated a sizeable resource of tumor tissue for further analyses. Our ongoing studies will use this resource as well as newly acquired tumor specimens and paired normal tissue, derived from children treated on two new Children’s Oncology Group high-grade glioma studies, to define the genetic alterations that characterize pediatric malignant gliomas, as a basis for prioritizing novel targets for prognostic and therapeutic stratification. We hypothesize that categorization of these tumors by their genomic alterations and drug resistance phenotype will improve accuracy of diagnostic and prognostic assessments, and provide insights into novel therapeutic targets. To test these hypotheses, we have initiated studies with the following aims: 1) Assess the frequency, composition, and prognostic relevance of alterations in Akt and MAPK pathway activation in pediatric malignant gliomas; 2) Determine whether O6-methylguanine-DNA methyltransferase (MGMT) overexpression and promoter methylation are associated with progression-free survival, independent of alkylator therapy; 3) Define, on a genome-wide basis, the spectrum and prognostic relevance of genomic alterations in pediatric malignant gliomas, using high-density SNP microarray-based profiling. Relevant markers will be evaluated in the context of conventional prognostic factors, such as histology, to determine their utility for biologically classifying childhood malignant gliomas. Taken together, these studies will incorporate a unique resource of childhood malignant brain tumor samples to provide new insights into the molecular categorization of pediatric high-grade gliomas. This work will establish a foundation for risk-adapted stratification and treatment planning, and the design of future therapeutic strategies for children with these tumors.

2) Molecularly Targeted Therapies for Malignant Gliomas

The limited response of malignant gliomas to conventional therapy reflects resistance to undergoing apoptosis in response to DNA damage or mitogen depletion, resulting from tumor suppressor gene mutations and aberrant activation of growth factor signaling. However, our previous studies indicated that despite the limitation in apoptotic triggering, effector pathways of apoptosis may remain intact and can be activated by inhibiting growth factor-mediated signaling or stimulating death receptor pathways. These studies also demonstrated that although a subset of gliomas were responsive to modulation of individual signaling pathways, many showed incomplete growth inhibition, reflecting activation of parallel pathways or intrinsic resistance mechanisms. This led us to examine the efficacy of combinatorial strategies for signaling inhibition, using agents targeting distinct pathways. Our initial studies suggested the potential for intriguing, synergistic interactions between signaling modulatory approaches, such as inhibition of PKC and Raf or JAK/STAT, and activation of apoptotic signaling by TRAIL, and with conventional therapies. Based on our findings, we hypothesized that therapeutic approaches that block rationally selected combinations of growth signaling pathways or that enhance apoptosis signaling will provide a novel strategy for inducing glioma cytotoxicity. To test this hypothesis, we are examining the effects on glioma growth and viability of inhibiting combinations of parallel pathways that transmit proliferative signals from aberrantly activated upstream receptors. These studies incorporate a panel of cell lines with defined genetic alterations to assess whether genotypic features influence efficacy, and establish biological surrogates of response. Second, we are determining whether signaling mediators that promote caspase expression can enhance apoptosis induced by stimulation of death receptor pathways by TRAIL, and evaluating biological factors that predict efficacy. Third, we are examining whether signaling modulation can enhance efficacy of radiotherapy and conventional chemotherapy in all, or a genotypically defined subset of, gliomas. These studies will provide a foundation for the translation of signal transduction inhibition and death receptor activation as therapeutic approaches for gliomas, and indicate ways in which these strategies can be used to enhance efficacy of other therapies.

3) Vaccine Therapy for Pediatric Gliomas

Diffuse brainstem gliomas, other malignant astrocytomas, and recurrent low-grade gliomas and ependymoma carry a poor prognosis, and new therapies are needed. Having gained experience with immunotherapy for adult gliomas, we extended these insights to childhood gliomas, based on our observations regarding their profiles of glioma-associated antigen (GAA) expression. We initiated a pilot trial of subcutaneous vaccinations with peptides for GAA epitopes emulsified in Montanide-ISA-51 given every 3 weeks for 8 courses along with intramuscular injections of poly-ICLC in HLA-A2+ children with newly diagnosed brainstem gliomas (BSG), high-grade gliomas (HGG), or recurrent gliomas. GAAs were EphA2, IL13Rα2, and survivin. Among 33 patients enrolled through June 30, 2012 (to allow a minimal follow-up duration of at least 9 months (last update 5/7/13) or until disease progression or off-study criteria were met); 14 had previously untreated BSG treated and received irradiation alone, six had newly diagnosed BSG treated with irradiation and concurrent chemotherapy, four had recurrent high-grade glioma, four had newly diagnosed high-grade glioma treated with irradiation and concurrent chemotherapy, and five had multiply recurrent low-grade glioma, after failure of numerous prior regimens. Patients have received 1-12 courses of therapy (median 7) to date. The primary objectives of this study were to assess immunologic response and safety, given that this was the first such trial in the pediatric age group. Principal toxicities have included local injection site reactions and low grade fevers and flu-like symptoms in almost all patients, referable to the poly-ICLC, which have been generally mild and controlled with To date, there have been 7 cases of at least possible immunologically-mediated pseudoprogression. Among 33 patients noted above, the best radiographic response has been stable disease through at least two vaccine cycles in 24, persistence of NED status after a prior gross total resection in 1, partial (>50%) response in 2 and minor response in 3. Only three patients had disease progression during the initial two cycles of therapy, including two brainstem glioma patients who were found to have metastatic disease on their first on-treatment MRI. Sixteen of 25 newly diagnosed patients had survived between 11 and 29 months after diagnosis (median survival: 413 days (13.6 months) in the overall cohort; 406 days (13.3 months) in the newly diagnosed BSG subset).

ELISPOT analysis has been completed to date in 22 newly diagnosed children with evaluable samples, and 14 showed response to at least one antigen at one or more study-defined time points (IL13Rα2 in 10, EphA2 in 11, and Survivin in 3). One child that had a sustained PR had striking persistence of ELISPOT response to IL13Rα2 extending over 33 weeks of vaccination. 

More extensive analyses of efficacy in a multi-institutional context are being planned within the Pediatric Brain Tumor Consortium. NIH funding has also been obtained for a study of this vaccine strategy in children with recurrent ependymomas.