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Hematology and Oncology

Cancer Predisposition Clinic Aims to Change the Trajectory of Genetically Based Cancer

Li-Fraumeni syndrome. Von Hippel-Lindau. Rhabdoid tumor predisposition syndrome. Beckwith-Wiedemann syndrome. Retinoblastoma.

These are just a few of more than a dozen rare genetic conditions that predispose a child to cancer. Overall, at least 10% of children with cancer harbor a disease-associated pathogenic variant in a known cancer predisposition gene. While few can be prevented, regular surveillance can, at the very least, find malignancies early when treatment is most effective.

That’s the idea behind Children’s of Alabama’s Cancer Predisposition Clinic, now in its third year.

“We  provide comprehensive care and screening for these patients with the goal of detecting cancers at an early stage in order to provide the best care and outcomes for the patients,” said Elizabeth Alva, M.D., assistant professor in the University of Alabama at Birmingham (UAB) Division of Pediatric Hematology and Oncology. “It used to be there was nothing we could do about this terrible diagnosis,” she said. “Now we know there are definitely ways to look for cancers early and help patients.”

In addition, the clinic provides psychological support for families and determines if the genetic condition affects other family members, she said.

Typically, primary care physicians follow children with cancer predispositions. But those doctors may not be aware of or able to provide the level of evidence-based surveillance that Alva offers.

That’s why these clinics are a growing area in the pediatric hematology/oncology world, particularly at the larger children’s hospitals. “We felt that we definitely needed to provide that same level of care here in Alabama,” Alva said.

Alva and neuropsychologist Avi Madan-Swain, Ph.D., are currently following about 25 patients. Patients come to them through the pediatric cancer genetics clinic, where families are tested and counseled. Alva provides the screening, which ranges from regular ultrasounds to CT scans and MRI, while Madan-Swain addresses the family’s psychological needs.

One benefit to the clinic is that if there is a cancer diagnosis, the child and family are already comfortable with the hospital and the clinical team.

Alva is building a database of patients to gain a better understanding of disease development and progression, while Madan-Swain plans research around the psychological impact on families that have a child with a predisposition syndrome.

Understanding Genes
Learn more about the UAB Department of Genetics.

Hematology and Oncology

The Institute for Cancer Outcomes and Survivorship Focuses on Key Quality-of-Life Issues


As more patients—adult and pediatric—become long-term cancer survivors, it becomes ever more imperative to identify ways to prevent, or at least manage, long-term complications from the cancer and its treatment.

Just how to do that forms the cornerstone of the research conducted at the University of Alabama at Birmingham (UAB) School of Medicine through its Institute for Cancer Outcomes and Survivorship (ICOS). “We are interested in developing a strong base of researchers who are focused on studying cancer outcomes long-term and identifying the issues cancer survivors face,” said ICOS Director Smita Bhatia, M.D., MPH. “We are continually striving to improve the quality of life of cancer survivors.”

Diverse Group

A diverse group of researchers from UAB participates in ICOS, including epidemiologists, physician scientists, behavioral scientists, molecular biologists and nurse scientists. They come from numerous departments, including radiation oncology, medical and pediatric oncology, and surgical oncology. Within ICOS, they have access to a state-of-the-art infrastructure that supports outcomes research, thus facilitating the transitional research that is integral to the Institute’s mission.

“The overarching goal of the ICOS is to conduct cutting-edge research in cancer outcomes across the age spectrum,” Bhatia said.

Since its founding in 2015, Institute researchers have received more than $10 million in grants from the National Institutes of Health and private foundations, and published more than 250 papers in peer-reviewed journals, a third of them high-impact journals.

Asking the Right Questions

All research studies start with asking the questions that no one has asked before, Bhatia said. “Questions are definitely going to move the field forward and make people’s lives better,” she noted.

For instance, a current study is examining long-term morbidity in pediatric cancer survivors, 60 percent of whom will eventually develop complications related to their cancer treatment. “We are systematically studying the molecular basis of these long-term complications,” Bhatia said.

Questions include: Why does radiation increase the risk of other cancers? How does a child’s DNA make them more prone to radiation-related cancers? Are there ways to predict children who are more likely to develop  treatment-related conditions and find alternative treatments to attack their cancer?

The Institute is also studying adherence to oral chemotherapy. “We find that children with acute lymphoblastic leukemia (ALL) often don’t take their medications as directed,” increasing their risk of relapse, Bhatia said. “We are now testing strategies to improve adherence to oral chemotherapy.”

To explore the impact of radiation and chemotherapy on the developing brain, researchers are using MRI to identify cellular signs of “chemo brain” and looking for ways to protect the brain during treatment.

“When a new patient comes in with cancer, the first thing we have to do is get rid of that cancer,” Bhatia said. That typically means using agents known to increase the risk of neurocognitive deficits. “So we have to develop methods to reverse or halt these complications.”

Several other research questions are under investigation, including ways to:

  • Expand the HPV vaccination rates in childhood cancer survivors
  • Determine the burden of morbidity older cancer survivors experience
  • Understand the best way to treat older patients with cancer without causing undue toxicity
  • Improve end-of-life experiences for cancer patients

Understanding ICOS Research
Learn more about ICOS research and watch an interview with Smita Bhatia, M.D., MPH.

Hematology and Oncology

Developmental Therapeutics Offers Next Generation of Cancer Medicines


One of the most devastating things a doctor has to do is inform a family that their child with cancer has run out of options. At Children’s of Alabama, however, clinicians often have one more thing to offer: access to early-stage clinical trials for potentially lifesaving drugs through its Developmental Therapeutics Program.

“Development therapeutics is about the next generation of medicines that will hopefully improve outcomes and reduce side effects for children with cancer,” Program Director Gregory Friedman, M.D., said.

Children’s is able to provide access to investigational compounds because it is one of just 21 pediatric oncology programs in the country invited to participate in the Children’s Oncology Group Phase 1 and Pilot Consortium. Consortium studies, Friedman said, “are how we’ve improved survival rates in recent years.”

Studies offered through the Developmental Therapeutics Program are generally Phase 1 or Phase 2 trials designed to demonstrate proof of concept, safety, tolerability and efficacy of new compounds. Currently, the program is managing more than 40 such studies.

Friedman is also developing a translational program to quickly move investigator-initiated research from laboratories at the University of Alabama at Birmingham (UAB) and Children’s into the clinical setting by providing an interface between the investigators and regulatory bodies, including the Food and Drug Administration. In addition, the Developmental Therapeutics team works with industry to develop new agents and is exploring participation in disease-specific pediatric consortiums.

Through the Developmental Therapeutics Program, Children’s also participates in the NCI-COG Pediatric MATCH trial, the largest precision medicine trial of its kind, in which tumor tissue is sent to the NCI for molecular testing to identify genetic abnormalities driving cancer growth. The goal is to then identify investigational or existing drugs to target those abnormalities and conduct clinical trials of the agents.

Friedman stresses that it takes a team to run the program including other physicians, a nurse manager, a clinical trial specialist, a data information coordinator and regulatory experts.

The goal, he said, is to continue to grow the program. “Our ultimate goal is to have a trial available for every child and family in these very difficult situations where few treatment options exist,” he said.

Viral Therapy in Malignant Brain Tumors Offers Hope

Developmental Therapeutics Program Director Gregory Friedman, M.D., is the principal investigator on one of the most exciting studies underway in pediatric cancer: evaluating the use of a cold sore virus to treat children with progressive malignant brain tumors. The approach is based on the finding that pediatric brain tumors are highly sensitive to genetically engineered oncolytic HSV-1 G207, which lacks genes essential for replication in the normal brain. The Phase 1 trial is designed to evaluate the safety, tolerability and preliminary efficacy of G207 delivered directly into the brain via intratumoral catheters.

Friedman and his team presented preliminary results on the treatments effects during the International Symposium of Pediatric Neuro-Oncology Meeting in Denver in June 2018. There were no dose-limiting toxicities or serious adverse events related to the virus and five of the six patients who received treatment demonstrated positive responses. One patient is now more than 21 months out from the treatment with a significant improvement in their well-being.

Since then, at least three other children have been treated safely with evidence of favorable drug activity. The next phase of the study will test the treatment’s safety in combination with a single dose of radiation, which is designed to enhance an immune response against the tumor.

Cancer Fighters
Learn more about the Alabama Center for Childhood Cancer and Blood Disorders.

Hematology and Oncology

A Holistic Approach to Childhood Cancer Survivorship


Significant improvements in pediatric cancer management means that an estimated 84 percent of children and adolescents diagnosed with cancer will become long-term survivors. However, while they may have overcome their original malignancy, they have a high risk of complications, including impaired growth, heart and lung problems, secondary cancers, learning disabilities and vision or hearing problems.

Yet, said Smita Bhatia, M.D., MPH, who directs the Institute for Cancer Outcomes and Survivorship at the University of Alabama at Birmingham (UAB) School of Medicine, “Research shows that primary care physicians are reluctant to take care of cancer survivors because these survivors have so many treatment-related complications. Often, these kids fall through the cracks.”

That’s where the Taking on Life After Cancer (TLC) survivorship program comes in. It focuses on improving the health and well-being of childhood cancer survivors and is the only clinic of its kind in Alabama.

“There is an increased need to provide care tailored to the long-term survivors of pediatric cancer,” said the program’s Medical Director Kimberly Whelan, M.D., MSPH. Not only are they at increased risk for numerous medical problems, she said, but they also often experience neurocognitive issues that can impact their schooling or job performance. “We strive to look at them holistically and see how they’re doing physically, emotionally and mentally, and give them the tools they need to succeed in life.”

When the clinic began in 2004, patients were seen just once starting two years after their last treatment. Today, patients are seen annually. “We learned that following them long term is important because the issues they face two to three years after treatment are different than the ones they may face five or 10 years after therapy,” Whelan said.

Wendy Landier, Ph.D., RN, CRNP, manages the clinical aspects of a patient’s visits. During the one-day visit, patients and their families see a physician or nurse practitioner who specializes in survivorship care, as well as a social worker to help with any issues related to costs and insurance. A neuropsychologist screens for problems with school or job performance. “The visit is tailored to meet the individual needs of each survivor,” she said. “For instance, educational materials are personalized so they address the specific treatment that each survivor received, as well as the potential complications that can arise as a result of that treatment.”

Patients also have the opportunity to participate in research studies designed to advance knowledge about survivorship issues. “We’re trying to learn more about why some survivors have certain complications and others don’t, and to develop mechanisms to reduce those complications,” Whelan said.

All visits are tailored to the individual child, their cancer and previous treatments. So a child who previously received radiation therapy to the chest, for instance, will undergo tests to assess lung and heart function. Other children may need their bone health checked regularly.

One task the clinic doesn’t do is screen patients for any recurrence of the original cancer, Whelan said. “So maintaining their relationship with their primary oncologist is important,” she said.

Patients are referred by their primary care physician or self-refer, Whelan said. Either way, the patients’ primary doctor receives summary reports. “We would love to partner more with the primary care physicians in the care of these patients,” she said.

The clinic currently follows about 500 patients, with another 100 added each year. All can be seen for the rest of their lives, regardless of age. “Our goal is to make sure they stay healthy,” Whelan said.

Dealing With a Cancer Diagnosis
Learn about Children’s of Alabama’s Hope and Cope Psychosocial Program.