Children with Localized Non-Germinomatous Germ Cell Tumors May Benefit from Reduced-Volume Radiation

Early results from a phase II trial of response-based, reduced-volume radiation therapy for pediatric patients with localized non-germinomatous germ cell tumors indicate that reducing radiation volume by targeting treatment to the whole ventricle could be considered, but with a higher risk of failure, in particular within the spinal canal. Results will be presented at the 2018 ASTRO Annual Meeting in San Antonio.

Non-germinomatous germ cell tumors have the potential to spread anywhere cerebral spinal fluid flows. “Classically, patients with non-germinomatous germ cell tumors receive induction chemotherapy then radiation to their whole brain and spine,” says Erin Murphy, MD, Director of Pediatric Radiation Oncology at Cleveland Clinic.

Still, whole brain and spine radiation can impact a patient’s long-term quality of life, potentially adversely affecting physical growth, neuro-cognitive development and hormonal regulation, and increasing the risk of secondary cancers. “With reduced-volume radiation, we don’t see as much of those effects,” Dr. Murphy says.

Reducing radiation volume

As a co-principal investigator for clinical trial ACNS1123, Dr. Murphy and her team set out to determine if patients with non-germinomatous germ cell tumors who responded well to induction chemotherapy would also experience improved outcomes with reduced-volume radiation therapy. In the trial, pediatric patients age 3 to 21 with non-germinomatous germ cell tumors who experienced partial or complete response after induction chemotherapy received radiation limited to the whole ventricle in a dose of 36 Gy and a total boost of 54 Gy to the primary site, five days per week for six weeks.

Non-germinomatous germ cell tumors are rare. “Radiation oncologists may only treat one or two of these kids a year,” Dr. Murphy says.

For increased precision in this study, radiation oncologists across multiple institutions used an online contouring atlas to provide high-quality radiation therapy. “The online contouring axis made radiation delivery more reproducible and ensured that radiation oncologists were targeting the appropriate cerebral spinal fluid space and avoiding normal structures,” Dr. Murphy says.

The study found that at three years, progression-free survival was 88 percent and overall survival was 92 percent. Those results are being compared to a previous clinical trial performed by the Children’s Oncology Group, ACNS0122, in which pediatric patients with non-germinomatous germ cell tumors received the same induction chemotherapy, followed by radiation to the whole brain and spine, resulting in higher volume radiation. Five-year progression-free survival for ACNS0122 was 92 percent; five-year overall survival was 98 percent.

“The early survival data from ACNS1123 is encouraging, but with the caveat that longer follow-up of these patients is necessary to better inform future treatment guidelines,” Dr. Murphy says.

Focusing on failure patterns

It is particularly noteworthy that eight patients participating in ACNS1123 failed in the spinal canal, outside of the radiation field. “We found that all eight patients had distant failure in the spine, which is significant because it’s a different pattern of failure than seen in other studies,” Dr. Murphy says.

The findings suggest that the spine is a risk for recurrence when only the ventricle and primary tumor are targeted with radiation.

Overall, the results of ACNS1123 are controversial. “Some oncologists want to reduce treatment to improve the long-term quality of life for these kids. But that could be at the risk of more kids failing and requiring additional intense treatment,” says Dr. Murphy, who is in the process of developing radiation treatment guidelines for non-germinomatous germ cell tumors.

At this juncture, the guidelines will indicate that reduced-volume radiation can be considered, but with a higher risk for failure. Until more evidence is in regarding the safety of this radiation protocol, “it’s important to discuss the treatment option with a multidisciplinary oncology team when making treatment recommendations,” Dr. Murphy says.