Modern, aggressive treatments for high-risk neuroblastoma have dramatically improved survival rates for what was once a pediatric cancer with a grim prognosis. However, the very therapies that save lives are leaving a legacy of serious and chronic health problems that can last a lifetime. A landmark study, the first to systematically evaluate the long-term outcomes of patients treated with contemporary protocols, reveals that a majority of survivors experience substantial late effects, including widespread hearing loss, growth failure, and pulmonary disease.
This new research provides a critical roadmap for the lifelong care these survivors will require. As survival rates have climbed over the past two decades, thanks to the integration of multiple stem cell transplants and immunotherapy into intensive chemotherapy regimens, a growing population of patients is now navigating adulthood with complex medical needs. The findings underscore an urgent need for diligent, ongoing surveillance and updated clinical guidelines to mitigate the quality-of-life impact of these treatments and address health challenges as they emerge.
A New Era of Survival and Scrutiny
Over the last 20 years, the standard of care for high-risk neuroblastoma has evolved significantly. Previously, the five-year survival rate for this aggressive childhood cancer, which most often appears in children under 5, was less than 25%. Today, with a multi-modal approach that includes high-dose chemotherapy, multiple stem cell transplants, radiation, and immunotherapy, the estimated three-year event-free survival rate has risen to 66% for patients who complete the full course of therapy. This success has created a new generation of survivors, but the long-term consequences of their treatment have not been well-documented until now.
To address this gap, researchers conducted a major study involving 375 survivors of high-risk neuroblastoma. The participants were enrolled between 2017 and 2021 from 88 hospitals participating in the Children’s Oncology Group (COG) across North America, Australia, and New Zealand. Eligible survivors were between 5 and 50 years old at the time of enrollment and had been diagnosed on or after January 1, 2000, ensuring the cohort reflected the effects of modern therapeutic strategies. This work represents the first seminal study to provide data on the late effects of these newer, more intensive treatments.
The Broad Spectrum of Late Effects
The study, published in The Lancet Child & Adolescent Health, paints a sobering picture of the health burdens carried by survivors. Researchers found that most participants had at least two clinically important late effects, and the prevalence of these conditions increased with longer follow-up time. The complications spanned a wide range of body systems, from sensory and developmental to endocrine and organ function.
Hearing Loss and Physical Development
The most common late effect identified was hearing loss. Of 327 participants assessed, a striking 72% had moderate-to-severe hearing impairment. This is a well-established side effect of the platinum-based chemotherapy agents that are crucial for treating neuroblastoma. Such a high prevalence of hearing loss has profound implications for a child’s educational development and quality of life, necessitating early intervention and support.
Perhaps more surprising was the impact on physical growth. More than half of the survivors in the study, 51% of 373 participants, were underweight. Furthermore, 24% of 360 participants were diagnosed with growth failure. Researchers noted that being underweight likely contributes to stunted growth. This pattern is considered a sign of accelerated aging, a phenomenon often seen in childhood cancer survivors that puts them at a higher risk for developing chronic health problems typically associated with older age.
Organ System and Endocrine Complications
The intensive therapies also took a toll on other organ systems. Pulmonary function tests revealed that 8% of 207 participants had restrictive lung disease, a condition that limits lung capacity. The risk for both growth failure and lung disease was higher in patients who had undergone multiple stem cell transplants compared to a single transplant. In a positive finding, the addition of immunotherapy to treatment regimens was not associated with an increase in the late effects measured in the study.
Other research supports these findings, showing a high number of late effects across the survivor population. One study of 61 survivors who had high-dose chemotherapy with stem cell rescue found that 86.9% developed late effects that worsened over time. Beyond hearing loss, these included endocrine problems (18%), orthopedic issues (14.8%), dental effects (27.9%), and renal dysfunction (3.9%), among others.
The Evolution Away from Irradiation
In an ongoing effort to reduce long-term harm, clinicians have also modified treatment protocols by moving away from total body irradiation (TBI) as a conditioning regimen for stem cell transplants. TBI was known to cause significant toxicities, and studies confirm that its avoidance has successfully reduced the incidence of certain late effects. Survivors treated with TBI have significantly higher rates of growth hormone deficiency, cataracts, and poor bone outcomes compared to those treated without it.
However, the elimination of TBI has not eliminated long-term morbidity. Survivors who receive high-dose chemotherapy and localized radiation still face a substantial burden of health issues. Research on a cohort of 48 survivors found that all of them, regardless of TBI exposure, had numerous late effects, with 73% having between five and ten distinct chronic health problems. This highlights that even the most modern, TBI-sparing regimens are intensely toxic and require careful, long-term follow-up.
Updating Guidelines for Lifelong Care
The clear and comprehensive data from these studies are set to directly influence clinical practice. The findings from the large COG study will be used to update the organization’s official guidelines for the care of childhood cancer survivors. These guidelines specify the risk-based screenings and preventative care that survivors should receive throughout their lives based on the specific treatments they were exposed to. The high prevalence of hearing loss, growth failure, and underweight status will likely lead to recommendations for more vigilant screening in these areas.
Experts emphasize that a multidisciplinary care team is essential for managing the complex health needs of high-risk neuroblastoma survivors. Lifelong, diligent surveillance is not just recommended but necessary to catch and manage these late effects early. As more children survive this disease, the focus of the medical community is expanding from not only curing the cancer but also ensuring survivors can lead long, healthy, and productive lives.
