Expert Emphasizes Importance of Collaboration for Rare Pediatric Cancers

Matthew Ladra, MD, MPH

Esthesioneuroblastoma is a rare malignancy of the paranasal sinus that occurs mostly in adults, though there is a small population of pediatric patients diagnosed annually. There is a significantly lower incidence of this disease in pediatric and adolescent patients, resulting in a lack of data and no standardization of therapy, according to Matthew Ladra, MD, MPH.

Radiation therapy is often used to treat adults with esthesioneuroblastoma, but it has shown to cause significant morbidity in pediatric patients. Currently, clinicians use a combination of surgery and chemotherapy, and sometimes radiation in extensive-stage cases, explained Ladra. Pediatric patients with early-stage disease can often receive surgery alone. However, a multimodal approach seems to confer the most benefit in the limited data available.

Ladra emphasized the importance of collaboration in the quest to find curative treatments for this malignancy. More data need to be collected to determine the true impact of chemotherapy on these patients, as well as surgical margins after endoscopic surgery versus interior cranial facial resection. Sharing data between institutions and collaborative groups is the most logical place to start, he added.

OncLive: Please provide some background information on esthesioneuroblastoma.

In an interview with OncLive, Ladra, director, Pediatric Radiation Oncology, assistant professor, Radiation Oncology and Molecular Radiation, Johns Hopkins Kimmel Cancer Center at Sibley Memorial Hospital, discussed the treatment of patients with esthesioneuroblastoma, emphasizing the need for collaboration in this rare malignancy.Ladra: This is a disease that occurs in the nasal cavity from neuronal tissue. It arises anywhere that there is olfactory epithelium. It most commonly occurs in adults, but about 20% of cases are in pediatric patients between 10 and 20 years of age.

How is treatment for these patients determined?

Being a very rare tumor, there is only about 63 cases described in the literature since 2000. Between the year 1900 and 2000, there were less than 100 cases described. Therefore, when we can get data from a multicenter collaborative effort, that is always very useful. In 2016, there was a study published with data from St. Jude Children's Research Hospital, Boston Children's Hospital, and Baylor University, which did a very good job of putting together these rare cases. They gave a summary of the outcomes for about 24 children using chemotherapy, radiation, and surgery in some combination. There are a couple of stages based on the clinical presentation and how invasive it is in the nasal cavity, or what it looks like under the microscope. Based on current staging, the treatment can range from surgery alone—which is for the earliest-stage tumors—to radiation if the tumor is larger and takes up more than one side of the nasal cavity or if it looks aggressive under the microscope.

What are the outstanding challenges in treating patients with this rare malignancy?

In pediatrics, there has been good response; between 60% and 80% of cases respond to chemotherapy. We have been using a combinatorial therapy of radiation, chemotherapy, and surgery, which appears to give the best results. In adults, the data for using chemotherapy is less compelling. In earlier stages, we will use surgery or surgery plus radiation. Chemotherapy is only for metastatic or extensive-stage disease in adults at most centers.[We need] more data. Since it happens so rarely, most people only see 1 or 2 cases in their career. The way in which we treat this is not standardized, so there are still a lot of questions. There are questions: how much benefit does chemotherapy bring? If it is a lower-grade tumor, do they need chemotherapy? Do they need radiation if they have had a good resection? How reliable are surgical margins after endoscopic surgery, which is going in through the nose, versus an interior cranial facial resection where you remove the tumor in total along with the surrounding bone and soft tissue structures?

What would you like oncologists to know about the landscape of this disease?

I can give guidelines based on existing research, but those are all based on series of 8 to 20 children, so we need to focus on collaborative efforts and sharing data. Also, we should come up with a good standardized agreement on how we should start treating these children at this point. Collaboration is the key to what we do, and to make things better in the future. Fortunately, the proportion of children who have cancer is so much smaller than adults. Using good studies and solid data to make changes, sharing our data, working together, and communicating is really what is going to make a difference.