Santhosh Upadhyaya, MD, neuro-oncologist, St. Jude Children’s Research Hospital, discusses drug development for pediatric patients with brain tumors.

Drug development is challenging, explains Upadhyaya, especially as it relates to pediatric patients with brain tumors because there is always a concern over blood-brain barrier penetration. In the 10-year-long SJYC07 trial presented at the 2018 ASCO Annual Meeting, results revealed that children with molecularly defined ependymoma and other malignant brain tumors under the age of 3 responded well to radiation therapy. Though the trial showed that children can be safely treated with radiation to improve outcomes, new drugs are needed.

Once a drug is developed and a trial is designed, collaboration is key, notes Upadhyaya. Physicians hope that through this collaboration, new medications will be discovered that target the pathways that are present in pediatric ependymomas.

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Dr. Upadhyaya Discusses Drug Development for Pediatric Patients With Brain Tumors

Santhosh Upadhyaya, MD, neuro-oncologist, St. Jude Children’s Research Hospital, discusses risk factors for developing pediatric ependymoma.

Most pediatric patients who are diagnosed with ependymoma are diagnosed without any known predisposition to the cancer other than neurofibromatosis, says Upadhyaya. Researchers have been unable to identify potential risk factors that lead to the development of the malignancy.

However, research regarding risk factors for relapse suggests that patients who have most of their tumor removed in surgery prior to receiving radiation have the best chance of cure. This is difficult to achieve, explains Upadhyaya, as these tumors are located in difficult-to-reach areas of the brain. Any aggressive attempt at resection may lead to neurological problems that may be permanent, Upadhyaya says. Using chemotherapy as a bridge in these situations may enable a patient’s tumor to shrink during the recovery process, potentially enabling them to undergo a second procedure.

Dr. Upadhyaya on Risk Factors for Pediatric Ependymoma

Santhosh Upadhyaya, MD, neuro-oncologist, St. Jude Children’s Research Hospital, discusses the importance of long-term follow-up in pediatric patients with ependymoma.

In the 10-year-long SJYC07 trial, researchers examined the use of radiation therapy for young children under the age of 3 with ependymoma. The trial reported that the use of chemotherapy and subsequent radiation is safe in treating residual cancer after surgical resection. However, Upadhyaya notes that the long-term side effects of radiation and chemotherapy are still a matter of concern. Specifically, neurocognitive deficits, endocrine issues, vascular problems, and potential secondary malignancies.

Therefore, patients who receive this protocol need to be closely monitored. At St. Jude’s, these children are monitored every 3 months with scans and physical exams. Visits are then extended to every 4 or 6 months based on the physician’s discretion and absence of recurrence. Long-term follow-up is especially important for patients with ependymoma, as those tumors can recur after the traditional 5 years of follow up.

Dr. Upadhyaya on the Importance of Long-Term Follow-Up in Pediatric Patients With Ependymoma

Santhosh Upadhyaya, MD, neuro-oncologist, St. Jude Children’s Research Hospital, discusses outcomes for children enrolled on the SJYC07 trial.

One of the most important goals on this trial, Upadhyaya says, was seeing if these children can be safely radiated starting at 1 year of age. Based on the trial results so far, Upadhyaya reports that it is possible. Children as young as 1-year-old with ependymomas can be safely treated with radiation to improve outcomes, he says.

The second most important consideration, Upadhyaya says, was whether radiation-deferring strategies could be used until a child’s brain matured to a point that radiation would be safe to use. Surgery and chemotherapy have been used as a bridge to get these children to 1 year of age, where they can then be treated with radiation.

Additionally, the presence of 3 molecularly distinct groups of ependymomas have been validated in this subgroup of patients, PF-A, ST-

-fused ependymomas are the more aggressive cases, these patients had better-than-expected results on the SJYC07 trial.

Santhosh Upadhyaya, MD, neuro-oncologist, St. Jude Children’s Research Hospital, discusses outcomes for children enrolled on the SJYC07 trial.
 

Dr. Upadhyaya on Outcomes for Children on the SJYC07 Trial

Santhosh Upadhyaya, MD, neuro-oncologist, St. Jude Children’s Research Hospital, discusses the design of the 10-year-long SJYC07 trial.

The trial examined the use of radiation therapy for young children under the age of 3 with ependymoma. The protocol first opened in December 2007 with the goal of improving outcomes for children under the age of 3 with highly malignant brain tumors at diagnosis, says Upadhyaya. The concept of the trial was to treat any remaining cancer after surgical resection with chemotherapy and subsequent radiation.

Physicians have known that radiation induces good outcomes in patients with ependymoma, but they did not know what the youngest age was that it could be used in. Another goal of the study, notes Upadhyaya, was to see if children as young as 1 year could receive radiation. Upadhyaya explains that patients in the trial are treated with 4 cycles of chemotherapy, after which neurosurgeons will determine if patients need another resection. Then, patients will receive radiation that specifically targets the tumor bed without exposure to the brain or the spinal cord.

Dr. Upadhyaya on the Design of the SJYC07 Trial in Pediatric Patients With Ependymoma

Santhosh Upadhyaya, MD, neuro-oncologist, St. Jude Children’s Research Hospital, discusses radiation therapy for young children under the age of 3 who have ependymoma. He highlighted outcomes of the 10-year-long SJYC07 trial at the 2018 ASCO Annual Meeting.

The trial, which began in 2007, tested children 3 years of age and younger who had molecularly defined ependymoma and other malignant brain tumors. Upadhyaya says that some of the main goals of the study were reached. The most important finding was that children younger than 3 generally responded well to radiation treatment.

Another focus of the trial was if differing radiation strategies could be used while a young child’s brain is maturing. A subgroup of patients under the age of 1 was treated with surgery and chemotherapy as a bridge before radiation started at 1 year old.

Upadhyaya says that the results are exciting and show that children can be safely treated with radiation to improve outcomes.

Santhosh Upadhyaya, MD, neuro-oncologist, St. Jude Children’s Research Hospital, discusses radiation therapy for young children under the age of 3 who have ependymoma.

Santhosh Upadhyaya, MD

Articles

Dr. Upadhyaya Discusses Drug Development for Pediatric Patients With Brain Tumors

Dr. Upadhyaya on Risk Factors for Pediatric Ependymoma

Dr. Upadhyaya on the Importance of Long-Term Follow-Up in Pediatric Patients With Ependymoma

Dr. Upadhyaya on Outcomes for Children on the SJYC07 Trial

Dr. Upadhyaya on the Design of the SJYC07 Trial in Pediatric Patients With Ependymoma

Dr. Upadhyaya on Radiation Therapy for Young Children with Ependymoma