Division Welcomes New Director of Neuro-Oncology Program

Alberto Broniscer, MD, MS, joined the UPMC Children’s Hospital of Pittsburgh Division of Pediatric Hematology/Oncology in August 2017. Formerly with St. Jude Children’s Research Hospital and The University of Tennessee Health Science Center (2002-2017), Dr. Broniscer has assumed the role of director of pediatric neuro-oncology at UPMC Children’s. He brings with him more than two decades of clinical and research experience, with expertise in conducting clinical trials and studying multiple aspects of brain and spinal cord tumors in children, including diffuse intrinsic pontine glioma (DIPG). A native of Brazil, Dr. Broniscer completed his medical degree and residency at the São Paulo University Medical School followed by fellowships at St. Jude Children’s Research Hospital, the New York University School of Medicine, and Johns Hopkins University School of Medicine.

As the new director of the nationally recognized neuro-oncology program at UPMC Children’s, Dr. Broniscer will be adding his tremendous talents and leadership to an already robust multidisciplinary clinical apparatus and a research program engaged in a diverse portfolio of clinical, translational, and basic science investigations.

“There are two key aspects of my work as director of the neuro-oncology program. First is the daily care of patients with brain and spinal cord tumors, to bring excellence of care to these individuals, collaborating to provide the most advanced treatment protocols possible in coordination with our colleagues in pediatric neurosurgery, radiation oncology, pathology, behavioral medicine, ophthalmology, and all the other members of the team,” says Dr. Broniscer.

The second aspect of Dr. Broniscer’s work central to his role as program director is a continuing focus on research to better understand the basic biology of brain and spinal cord tumors, and to develop new treatments that may lead to improved standards of care for these rare cancers. “With many of these rare diseases, we are lacking, as a field, standard treatments and paradigms for care. This is largely due to the rarity of the conditions, and our incomplete basic biological understanding for how and why these cancers arise in our pediatric patients.”
Current Research Highlights

Since arriving at UPMC Children’s in August, Dr. Broniscer has become involved in several clinical trials using immunotherapy (vaccines) for low-grade gliomas and recurrent ependymomas4-6, all of which are ongoing with patient recruitment. As a current member of the Pediatric Brain Tumor Consortium, Dr. Broniscer has been involved in many past investigations and is currently leading one national clinical trial studying immune checkpoint inhibitors in patients whose brain tumors contain large numbers of genetic abnormalities. “These are rare, deadly tumors that we are hopeful will show improved response to this recently FDA-approved agent being used in adult patients whose tumors have an excessive number of genetic abnormalities,” says Dr. Broniscer. 

DIPG and Plans for New Research

A significant portion of Dr. Broniscer’s past work has been related to the devastating diffuse intrinsic pontine glioma. Most likely the deadliest of all pediatric brain cancers, this aggressive brain stem malignancy remains incurable and difficult to treat due to its invasive nature in the pons and surrounding structures, which are areas that contain crucial basic life support functions. Current standards of care have changed little in the last three decades with radiotherapy being the accepted route to achieve temporary symptom reduction and a slowing of disease progression.

Progress has been made on several fronts in recent years, notably in the ability to safely biopsy these tumors, when warranted, which has allowed for an increase in tissue samples available to be analyzed. Routine biopsies are still typically not done for many reasons, although clinicians and researchers in France and some locations in the United States have begun to do this regularly in recent years. “These biopsies can be done safely, and I think in the future, we’ll be doing more of them, more frequently. As it stands right now, we simply do not have the tools to choose the best possible treatments based on the genetic findings from the tumor obtained at biopsy.⁷ This will change, I hope, soon, and then the benefits of biopsy will really become relevant as physicians may be able to adjust treatment based on actionable genetic findings in each tumor,” says Dr. Broniscer.

Past work by Dr. Broniscer and colleagues has revealed, in a study published in 2008, a different disease trajectory in individuals diagnosed with DIPG at a younger age. “In these individuals, we found that the biology of the tumors was markedly different than in cases of later onset. Younger patients with DIPG responded more favorably to the standard treatment; however, the end outcome is still fatal with this disease. This clinical observation was later validated by showing that DIPG in younger patients harbors different genetic abnormalities than tumors from older children,” says Dr. Broniscer.

Since his arrival, Dr. Broniscer has been working to design new research and clinical trials. “We are working to develop new studies of the biology of brain and spinal cord tumors in children, and to potentially design clinical trials for affected patients. To be here at UPMC Children’s, leading the neuro-oncology group and collaborating with so many of our other world-class departments and people, it’s an exciting time to be working in this field, and I’m privileged to help lead the way forward.”

References and Further Reading

A sample of Dr. Broniscer’s most recent publications and his current open clinical trials are below.

¹ Pinto EM, Hamideh D, Bahrami A, Orr BA, Lin T, Pounds S, Zambetti GP, Pappo AS, Gajjar A, Agnihotri S, Broniscer A. Malignant Rhabdoid Tumors Originating Within and Outside the Central Nervous System Are Clinically and Molecularly Heterogeneous. Acta Neuropathol. 2018 Feb 10. doi: 10.1007/s00401-018-1814-2. Epub ahead of print.
² Patay Z, Merchant TE, Nguyen R, Pierson CR, Onar-Thomas A, Broniscer A.Treatment-Related Noncontiguous Radiologic Changes in Children With Diffuse Intrinsic Pontine Glioma Treated With Expanded Irradiation Fields and Antiangiogenic Therapy. Int J Radiat Oncol Biol Phys. 2017 Dec 1; 99(5): 1295-1305. doi: 10.1016/j.ijrobp.2017.08.021. Epub 2017 Aug 24.
³ Kilburn LB, Kocak M, Baxter P, Poussaint TY, Paulino AC, McIntyre C, Lemenuel-Diot A, Lopez-Diaz C, Kun L, Chintagumpala M, Su JM, Broniscer A, Baker JN, Hwang EI, Fouladi M, Boyett JM, Blaney SM. A Pediatric Brain Tumor Consortium Phase II Trial of Capecitabine Rapidly Disintegrating Tablets With Concomitant Radiation Therapy in Children With Newly Diagnosed Diffuse Intrinsic Pontine Gliomas. Pediatr Blood Cancer. 2018 Feb; 65(2). doi: 10.1002/pbc.26832. Epub 2017 Nov 1.
⁴ Immunotherapy for Recurrent Ependymomas in Children Treatment for Recurrent Ependymomas Using HLA-A2 Restricted Tumor Antigen Peptides in Combination With Imiquimod. ClinicalTrials.gov Identifier: NCT01795313.
⁵ A Pilot Study of Glioma Associated Antigen Vaccines in Conjunction With Poly-ICLC in Pediatric Gliomas. ClinicalTrials.gov Identifier: NCT01130077.
⁶ A Vaccine Trial for Low Grade Gliomas. ClinicalTrials.gov Identifier: NCT02358187.
⁷ Biological Medicine for Diffuse Intrinsic Pontine Glioma (DIPG) Eradication (BIOMEDE). ClinicalTrials.gov Identifier: NCT0223