As a pediatric oncologist at the University of Chicago, Susan L. Cohn, MD, is passionate about improving outcomes for children with cancer, especially patients with neuroblastoma. She has devoted her career to developing more effective treatments for children with this disease, which is the most common type of cancer found in infants younger than age 1. For her dedication and commitment to the field, Dr. Cohn will receive the Pediatric Oncology Award and will deliver the award lecture on June 5.
Dr. Susan L. Cohn
Over the years, many strides have been made in the treatment of neuroblastoma. Dr. Cohn attributes these accomplishments to the power of collaboration, both nationally and internationally. “The pediatric oncology communities in North America, Australia, New Zealand, Europe, and Japan have a long-standing history of working together to develop and conduct cooperative group and multi-institutional clinical trials. These clinical trials have led to significant advances in treatment strategies and improved outcomes for children with neuroblastoma,” Dr. Cohn said. “I am accepting this award on behalf of all of my pediatric oncology colleagues, and my lecture will focus on what we have accomplished together.”
Evolution of a Leader
During her residency at the Michael Reese Hospital and Medical Center, Dr. Cohn realized that she wanted to care for children with cancer. She completed her clinical fellowship training in pediatric hematology/oncology at the Ann & Robert H. Lurie Children’s Hospital of Chicago (then known as Children’s Memorial Hospital) and was a research fellow at Northwestern University in the laboratory of Steven Rosen, MD, FACP, a medical oncologist. At the time, Dr. Rosen was investigating the role of the L-myc oncogene in small cell lung cancer.
Fortuitously, Dr. Rosen suggested that Dr. Cohn conduct a research study investigating the N-myc oncogene in neuroblastoma, a pediatric neuroendocrine tumor that shares biologic features with small cell lung cancer. Dr. Cohn made several discoveries about the role of N-myc (now named MYCN) amplification in unique cohorts of patients, including those with localized tumors and infants with stage IV-S neuroblastoma. This research set the stage for her career.
Dr. Cohn noted that neuroblastoma is a “cancer that has a broad spectrum of clinical behavior. Some infants have tumors that will spontaneously regress, whereas others [have tumors that] are highly curable with moderate-dose chemotherapy and surgery. In contrast, children older than 18 months with widely disseminated disease have clinically aggressive tumors that remain difficult to cure, even today.” The challenge for researchers has been to better understand the biological underpinnings of neuroblastoma so that treatment strategies can be tailored according to the predicted behavior of the tumor.
In 2000, as the newly appointed first chair of the Children’s Oncology Group (COG) Neuroblastoma Disease Committee, Dr. Cohn worked with her colleagues to address this issue by developing a risk-classification system based on a combination of clinical and biological prognostic markers for treatment stratification. Then, under Dr. Cohn’s leadership, a series of risk-based clinical trials were developed and conducted, resulting in significant reductions in treatments for children with low- and
intermediate-risk disease while maintaining excellent survival. One study showed that excellent results could be achieved with surgery alone in children with low-risk neuroblastoma.1 Another study found that patients with intermediate-risk neuroblastoma had a high rate of survival when given reduced doses of chemotherapeutic agents over a shorter timeframe compared with outcomes from the more intensive regimens used in earlier trials.2
In addition, clinical trials focusing on high-risk disease have led to steady increases in survival for children with more aggressive neuroblastoma. A seminal randomized study (ANBL0032) in patients with high-risk neuroblastoma demonstrated improvement in overall survival with a post-consolidation regimen of dinutuximab and isotretinoin compared to isotretinoin alone.3 This clinical trial ultimately led to the first U.S. Food and Drug Administration approval of dinutuximab in combination with interleukin-2, GM-CSF, and isotretinoin for patients with high-risk neuroblastoma.
Dr. Cohn had long recognized the need for international collaboration in the field. Ten years ago, she worked with Andrew Pearson, MD, MBBS, of The Royal Marsden NHS Foundation Trust, in the United Kingdom, and colleagues to develop an International Neuroblastoma Risk Group (INRG) Classification System, which was published in Journal of Clinical Oncology in 2009.4 The purpose of this system, based on the analysis of data from more than 8,800 patients, was to facilitate the comparison of clinical trials conducted in different regions of the world.
Soon realizing the value of this patient information, Drs. Cohn and Pearson developed a process to provide the data to investigators interested in conducting research studies. A number of seminal studies have been completed that would not have been possible without access to this large clinical data cohort. For example, an analysis of a cohort of patients with a rare, low-stage, MYCN-amplified neuroblastoma revealed that patients with hyperdiploid tumors had statistically significantly better outcomes than those with diploid tumors. These findings indicated that treatment could be reduced in the hyperdiploid group.5
In addition, analysis of a small subset of patients with metastatic disease limited to lymph nodes demonstrated that that these patients had better outcomes compared to other patients with metastatic disease, suggesting that less intensive therapy should be considered for these patients.6
More recently, the INRG data have been uploaded to a live database that accepts queries in a standard web format and is built with technology that enables connections to genomic data sources, such as information generated from the National Cancer Institute’s Therapeutically Applicable Research to Generate Effective Treatments (TARGET) initiative. Currently, germline genotype data on 1,662 patients from an ongoing genome-wide association study in neuroblastoma have been linked to the clinical INRG data. In addition, the database also includes tumor copy number data generated from infants enrolled in recently completed International Society of Paediatric Oncology European Neuroblastoma Research Network studies.
Multiple Contributions on the Homefront
As dean for clinical research in the Biological Services Division and acting section chief in pediatric hematology/oncology at the University of Chicago, Dr. Cohn has had an opportunity to make a difference on multiple fronts, including training the next generation of pediatric oncologists. She also co-directs the University of Chicago Institute for Translational Medicine, with Julian Solway, MD.
But she becomes particularly energized in the clinic. “I am inspired by my patients and their families to develop more effective therapies that will enable children with neuroblastoma to live high-quality lives for as long as possible,” Dr. Cohn said.