Dr. Sarah Gubara (Host): Welcome to Pediatrics in Practice, a CME podcast. Before we introduce our guest, I wanted to remind you to claim your CME credits after listening to today's episode. You can do so by visiting cmkc.link/cmepodcast and click Claim CME.

I'm Dr. Sarah Gubara. And today, I have with me Dr. Nikki Wood, pediatric hematologist and oncologist at Children's Mercy Kansas City. I invite you to listen in as we discuss pediatric genetic dispositions to cancer and what pediatricians need to know. Dr. Wood, thank you so much for being here today.

Dr. Nikki Wood: Hi. Thank you for having me.

Host: It is wonderful to have you. I'm really excited to get to know more about recognizing genetic cancer risk, referring to genetics appropriately and supporting families through this diagnosis.

Dr. Nikki Wood: Yes, absolutely. I'm excited to present this topic and these different nuances and details about it, and hopefully inform our pediatricians and help guide them on how to help these families.

Host: That's wonderful. Can you tell us more about what genetic predisposition to cancer means in pediatrics and how common it is in children with cancer or children with concerning family histories?

Dr. Nikki Wood: Yes, absolutely. So when we talk about genetic predisposition to cancer in children, we're referring to an inherited or sometimes de novo change in a gene that increases a child's risk for developing tumors over their lifetime. These genes are often involved in things like tumor suppression, DNA repair, and even cell growth regulation. It takes two hits to cause a cell to turn into cancer, and these kids already have one hit. Historically, we thought this accounted for about 5% of pediatric cancers. But with broader and more accessible genetic testing, we now estimate that closer to 10 to 15 or even more percent of children with cancer may have an underlying predisposition. So, this is not rare, and it's becoming an increasingly important part of pediatric oncology care.

It's also important to recognize that these conditions don't just predispose to malignant cancers. They can also lead to benign tumors, which can cause pretty significant morbidity depending on the location of them. So at Children's, we have a SPOT clinic, which is short for Surveillance for Predisposition to Tumors. It's co-led by myself and Dr. Kevin Gin. And we see conditions like Li-Fraumeni syndrome, Von Hippel–Lindau, hereditary paraganglioma-pheochromocytoma syndrome, and DICER1 just to name a few. Individually, each of these is rare. But collectively, they're something we see with increase in frequency, especially as more families undergo genetic testing.

Our SPOT clinic is part of our hem-onc clinic. It was actually established back in 2017, and it's grown significantly since then where we started with quarterly clinics and now we have monthly clinics and follow nearly a hundred patients, many of whom are siblings or relatives from the same families, which really reflects the nature of inherited risk.

Once a predisposition is identified, there's often a question of who follows these patients. And there is definitely some nuance there. In our SPOT clinic, we follow cancer predisposition syndromes associated with cancer risk and where there's evidence to support screening and we have screening protocols that we follow. Some patients, however, are followed in other specialties even though they have a cancer predisposition, depending on their specific risks and what symptoms they might have more. So, so as an example, NF-1 and NF-2, neurofibromatosis 1 and 2, or tuberous sclerosis patients are followed with neurology. PTEN or Cowden syndrome patients, patients with MEN are followed in endocrinology. And then, GI actually sees some of the GI cancer syndromes. And then, there are patients with bone marrow failure syndromes and hematologic risks. And that might also have other issues like cytopenias or coagulopathy. And these patients may follow in our general hematology clinic.

So, there's really a bit of a gray zone. And importantly, we don't expect pediatricians to know where each of these patients should go and be seen. Our recommendation is simple. If there's concern, refer to genetics or oncology and we will help direct the patient to the appropriate clinic based on our internal pathways.

One area we're particularly excited about, just to finalize and round out this question, is our work with families with Li-Fraumeni syndrome. We developed a collaboration with the University of Kansas Cancer Center, and Dr. Jeffrey Weitzel through the Heartland's Li-Fraumeni Syndrome Program. Many of our pediatric patients have parents or first-degree relatives that are also affected and require complex surveillance and treatment. So, this allows for a more coordinated family centered care and approach, and even opportunities for research. So, we're really excited about that specific cohort of patients regionally in our area.

Host: I love how collaborative and integrated your efforts are. It sounds like a wonderful clinic. What red flags in a child's personal history or physical exam or even their family history should prompt a pediatrician to think about a cancer predisposition syndrome?

Dr. Nikki Wood: This is a great question, and I love the proactive approach. I always frame it as recognizing when something doesn't quite fit, rather than trying to identify a specific syndrome. From a pediatrician's perspective, most of these conditions are not obvious early on, so we're really looking for patterns. Things that might prompt consideration for referral would be physical exam findings like café-au-lait spots, unusual birthmarks, overgrowth or congenital anomalies, developmental delays or neurologic differences that suggest an underlying genetic condition. And family history is important, so multiple relatives with cancer especially at younger ages, like less than 45, multiple cancers in one person or one relative, or patterns across the paternal or the maternal generations.

From an oncology side in a child with cancer, we also think about things like rare tumors, multiple tumors or unexpected treatment toxicity as indicators, but those are typically identified after diagnosis and things we're dealing with on the oncology side. And pretty routinely now in patients with cancer, we do paired somatic and germline testing to determine if a patient's cancer occurred from an inherited condition. So, the key takeaway is you don't need to diagnose this syndrome. If something feels atypical or doesn't quite fit, that's the right time to refer and let genetics help sort it.

Host: Now, I know you're really passionate about risk reduction strategies. Many families assume genetics only matters if there's a strong family history. Why can a child still have a genetic predisposition even when family history seems unremarkable?

Dr. Nikki Wood: Sure. Absolutely. And this is an important point, because many families assume that if there's no family history, there can't be a genetic cause. And that's not true in pediatrics. Many pediatric cancer predisposition syndromes are actually due to de novo mutations, meaning they occur for the first time in the child and are not inherited from either parent.

Actually, this is reported to be the case in about 7% to up to 20% of patients with Li-Fraumeni syndrome. In other cases, there can be reduced penetrance where a parent carries the gene but never developed or at least hasn't yet developed cancer. And increasingly, we're identifying these syndromes through testing done for other reasons like developmental delays or neurologic conditions where a cancer predisposition gene gets found incidentally. So, a negative family history does not rule out, and that's why we rely on the child's presentation and overall pattern rather than family history alone to guide whether further evaluation is needed.

Host: Wonderful. Dr. Wood, when should pediatricians refer to genetics? And what can families expect from a genetic counseling and testing visit?

Dr. Nikki Wood: This is important, because I don't want pediatricians to feel like they need to be out there actively hunting for these syndromes. Most of them are actually silent until they're not. In our clinic, many of the children we see are identified through cascade testing, meaning a relative, often a parent or a sibling, or a first-degree relative was found to have a genetic predisposition after say their cancer diagnosis, and then other family members were tested, and then the child lands in our clinic.

We also see some children I alluded to earlier who had broader genetic testing done for other reasons, like developmental delays, neurologic conditions, or congenital differences where a cancer predisposition gene is identified Incidentally. So from a primary care standpoint, the goal is really to recognize when something doesn't fit.

Some reasons to consider a referral to genetics would be concerning physical exam findings like café-au-lait spots, overgrowth, congenital anomalies, the developmental delays, or other features suggesting an underlying syndrome, or a family history, especially like I said, at ages that are younger and have those unusual patterns. So, those are super important. And I wanted to circle back to those.

That said, if the concern is family history alone, and this is super important, the most important first step is testing the person in the family who's had cancer since they're the most likely to have an identifiable mutation. Testing an unaffected child without that information is often not helpful. I always tell pediatricians, if you're unsure, that's the right time to refer. Our genetics teams are very used to triaging these referrals and helping determine who actually needs testing And what the next steps should be. So, our genetic counselors will call the family, and get a little bit more history. So, it's important to set expectations with families that a referral to genetics is to determine whether the testing is needed, not necessarily that the testing will happen.

Now, if testing is deemed necessary during a genetics visit, families can expect a detailed review of personal and family history, a discussion about the potential for genetic testing and guidance on what the results could mean. If testing's pursued, it's done thoughtfully with counseling before and after, so families understand not just the results, but how those results will impact care.

So, all that to say, if a pediatrician refers to oncology for a concern with a family history, it's usually our genetic counselors that work with us, that triage those, call the family, and determine whether that genetic testing is needed. Because to get into our clinic, they need to have that genetic testing confirm that they have a cancer predisposition syndrome.

Host: When a genetic predisposition is identified, how does surveillance change a child's care? And what role does the pediatrician play in supporting that long-term followup?

Dr. Nikki Wood: Yeah. So, as a reminder that child, if they're suspected or have a confirmed cancer predisposition syndrome, they're first evaluated by clinical genetics. And if that diagnosis is confirmed, they're then referred to the appropriate clinic for surveillance and ongoing care. So by the time those patients reach us, they already have that defined genetic diagnosis, and our role becomes focused on surveillance and long-term management.

Once that genetic predisposition is identified, care is much more proactive. Instead of waiting for symptoms, we use risk-based surveillance, which might include regular imaging, lab work, clinical exams to detect cancers as early as possible. It's not hard to imagine that treatment is often less invasive and more successful when tumors are identified at a smaller earlier stage, which is the goal for regular surveillance.

The pediatrician plays a critical role in patients with cancer predisposition syndrome. These children are followed long-term, often into adulthood, and pediatricians help ensure continuity of care, reinforce adherence to screening and support the family over time. They're really key partners in making sure these surveillance plans are actually carried out. They should be receiving a copy of our clinic notes, which have the screening recommendations that we're coordinating and following. We've also been working to add a section on what pediatricians can and should look for during their encounters with these patients based on the underlying diagnosis and what they're at-risk for.

So, sometimes that's making sure they're getting blood pressure checked at every visit, making sure they have thorough physical exams. Remember, cancer can happen anytime. So families are educated on things to look for in between their annual visits with us and when to seek care. So, they may show up at the pediatrician's doorstep with questions or needing a physical exam.

And in addition to surveillance, I personally talk about modifiable risk, so that includes environmental exposure, things like air quality, pesticide use, household chemicals, and definitely medical radiation, which should be limited in these patients unless medically necessary.

I offer practical guidance and resources for families. It's truly a way to complement the surveillance with prevention-focused care. And one thing that families often find helpful is having something they can do. That's where I sometimes incorporate this environmental health. I review exposures and offer simple risk reduction strategies so they can feel more empowered and more in control moving forward.

Host: I love that the education and resources you provide makes families feel more empowered, because these diagnoses can carry emotional and practical burdens for many families. So, Dr. Wood, how can pediatricians help families navigate the anxiety, the uncertainty, and the long-term nature of surveillance?

Dr. Nikki Wood: So these diagnoses, like you said, they can be overwhelming. They are overwhelming. And families are not only processing risks, they're often thinking about the future in a completely different way. And one of the most important things pediatricians can do is acknowledge that uncertainty and normalize those feelings.

I also try to reframe surveillance, not as something to fear, but as something empowering. It's a way we can act early and support better outcomes, and it truly does support better outcomes. So, partnering with families by helping connect them with the right resources, genetic teams, support groups, mental health services, can make a huge difference. This is not something families should have to navigate alone.

When we see patients in our clinic, we do provide psychology support. We have a provider and we screen for mental health effects of the associated stressors for these kids and families. Regular surveillance and the anticipation of potentially developing cancer is highly stressful, especially within families who often have multiple other affected individuals with their own surveillance and often treatment needs.

So, we provide screening at every visit to identify those who may have mental health needs that we can address, either through establishing care with our providers or through connections with the community mental health partners. So, pediatricians play a huge role in partnering with families with us on helping families navigate this difficult situation.

Host: Dr. Wood, thank you so much for answering our questions and helping us better understand cancer risk and navigating this complex and difficult time with many families.

Dr. Nikki Wood: Absolutely. Happy to be here. Happy to answer questions. And we are always open to fielding questions or concerns about these patients at any time during their care. At the end of the day, this work is about moving from uncertainty to action and helping families understand risk and giving them a path forward. And these cancer predisposition syndromes are common. They're often invisible and they're profoundly impactful. And the earlier we identify them, the more lives we save.

Host: Absolutely. As a reminder, claim your CME credit for listening to our show today. Visit cmkc.link/CME podcast and click Claim CME. This has been another episode of Pediatrics in Practice, a CME podcast. To refer your patients or for more information, please visit childrensmercy.org to get connected with one of our providers. Please remember to subscribe, rate, and review this podcast and all other Children's Mercy podcasts. Thank you for listening.