Key Findings from Children's Hospital of Philadelphia

Researchers at Children's Hospital of Philadelphia (CHOP) have put forward a new standard of care for families affected by hereditary neuroblastoma associated with the anaplastic lymphoma kinase (ALK) mutation. This rare form of cancer, which primarily impacts children, has shown promising responses to targeted ALK inhibition therapies, as detailed in a recent publication in JCO Precision Oncology.

Current Challenges in Neuroblastoma Treatment

Despite advancements in treatment for high-risk neuroblastoma, the survival rate over five years remains troublingly low, at under 50%. Dr. Yael P. Mossé and her research team have established a connection between a significant number of familial neuroblastoma cases and the ALK mutation, which can be specifically tested and targeted for treatment.

Case Study Highlights

The study provides a detailed examination of a mother and daughter duo, both diagnosed with neuroblastoma and both carrying the ALK R1275Q mutation. Their treatment journey illustrates the potential of targeted ALK inhibitors in achieving long-term remission. The daughter, diagnosed at six months, initially underwent standard chemotherapy and surgery, which were unsuccessful. However, after a recurrence, she showed remarkable improvement with the ALK inhibitor crizotinib.

The mother, who had been asymptomatic, was diagnosed with bilateral adrenal tumors during pregnancy at the age of 36. After delivering her child, she began treatment with crizotinib and later switched to a different ALK inhibitor, alectinib, due to side effects. Post-surgery to remove the tumors, she continued with alectinib and has remained in remission for several years. Both mother and daughter are now monitored biannually through whole-body MRI and circulating tumor DNA (ctDNA) testing, showing no signs of disease recurrence.

Recommendations for Future Treatment

The authors of the study believe their findings could fundamentally alter the treatment approach for hereditary neuroblastoma patients harboring the ALK mutation. They advocate for the use of ALK inhibitors as first-line therapy, which could minimize the reliance on intensive chemotherapy and invasive surgeries. Furthermore, they emphasize the necessity of lifelong monitoring for these patients, which contradicts current guidelines that suggest discontinuing surveillance after childhood.

Future Research Directions

Moving forward, the research team intends to investigate whether individuals with hereditary ALK mutations experience a reduced risk of developing drug resistance compared to those with non-inherited mutations. This line of inquiry could further refine treatment strategies and improve outcomes for patients facing hereditary neuroblastoma.

For additional details, refer to the original study by Yaël P. Mossé et al. in JCO Precision Oncology.