A pioneering clinic at UCLA Mattel Children’s Hospital is making a significant impact on the lives of children and their families with rare genetic conditions that predispose them to cancer, as well as those diagnosed with pediatric cancers that are potentially related to a rare genetic syndrome.
The UCLA Pediatric Cancer Predisposition Clinic was established in 2012, at a time when powerful new genetic testing technologies were first being implemented clinically at UCLA. This so-called next-generation DNA sequencing enabled, for the first time, comprehensive testing of all of the protein-coding regions of the genome to diagnose rare conditions and identify genetic predispositions.
“At the time, little was known about the utility of genetic testing in children with genetic syndromes that could predispose them to early cancers,” says Julian A. Martinez, MD, PhD, a clinical geneticist and the center’s codirector. “We believed it had potential value in that it would enable surveillance of patients with these predispositions to detect and treat the tumors early, as well as facilitating targeted treatments in patients already diagnosed with cancer based on the genetic cause identified.”
That initial vision has borne out, Dr. Martinez notes, and the clinic’s approach to patients with cancer-predisposing genetic conditions or cancers resulting from genetic syndromes has become the international standard for how such patients should be evaluated and managed. The clinic’s value has only grown with the continued advances in DNA sequencing technologies and the development of new treatments that target the specific genetic mutations underlying an individual patient’s cancer.
The UCLA Pediatric Cancer Predisposition Clinic remains one of the few multidisciplinary efforts of its kind, notes Vivian Y. Chang, MD, MS, a pediatric hematologist-oncologist and codirector of the clinic. The clinic brings together oncologists, geneticists, genetic counselors and social workers to provide diagnostic genetic testing and counseling, as well as personalized screening protocols as needed. All cases are discussed at a weekly genomic board meeting that includes bioinformatics specialists and pathologists, as well as clinicians.
Most of the clinic’s patients fall into one of two categories. The first are those who have already been diagnosed with a genetic syndrome associated with a high risk for developing a cancer. “My role as the oncologist is to educate these patients about their cancer risk and develop personalized cancer screening plans,” Dr. Chang explains. “We know that if we catch these cancers early, it offers the best prognosis and the best treatment options. We can now utilize targeted treatment for patients who are identified to have specific genetic mutations, whereas in the past, we had no specific treatments or we used broad-stroke chemotherapy and/or radiation to kill cancer cells. This is how we envision personalized medicine in the future for everyone.”
Dr. Chang has been a leader in developing surveillance guidelines for patients with underlying genetic syndromes that predispose to cancer risk, as part of an expert panel convened by the American Association for Cancer Research. “With these genetic diagnoses that are this rare, it’s important to share data across centers,” she notes. “By doing so, we have developed evidence-based guidelines so that these patients can be treated in a standardized way.”
The second major population of patients seen at the clinic are children — and in some cases, adults — who have already been diagnosed with a cancer, but certain features of their presentation or family history suggest an underlying genetic cause. Often, Dr. Martinez notes, these patients have gone through what is commonly referred to as a diagnostic journey, presenting with multiple medical conditions that have eluded a unifying diagnosis. “With our state-of-the-art genetic testing, we can put an end to the diagnostic journey so that these families are no longer making their way through the medical system, trying to find answers,” Dr. Martinez says. “We are able to provide a medical home for these patients and a roadmap for what to expect, in addition to better-informed treatment.” Ending the diagnostic journey brings multiple benefits, Dr. Martinez notes. For families, there is great psychological benefit to finding closure after a long, emotionally trying odyssey in search of an explanation for their child’s symptoms. That journey can include expensive and ultimately fruitless testing, at significant cost to both the families and the health care system. In some cases, the definitive diagnosis points to a condition that could affect other family members, who can then benefit from being tested and, if they test positive, being treated or more frequently screened, as appropriate.
Dr. Martinez says that roughly 10 percent of the pediatric cancer patients referred to the clinic have been found to have a well-documented genetic syndrome, and his team has described new syndromes along the way. Other centers that have followed the UCLA clinic’s approach have found, similarly, that about 10 percent of their pediatric cancer patients will have a known genetic disorder that can benefit from surveillance and personalized care.
For more information about the UCLA Pediatric Cancer Predisposition Clinic, email clinic manager Marcela Serrano at [email protected]