Pediatric low-grade gliomas: How diagnosis and treatment practices affect survival

Brain tumors represent the most common cause of death from a solid tumor in children. Although outcomes for patients with low-grade gliomas (LGGs) are considered good compared with those with high-grade tumors, many children with LGGs have a much shorter life expectancy than their healthy peers.

Over the past 40 years, diagnosis and treatment of LGGs have changed substantially. CT and MRI have revolutionized tumor imaging. Surgical procedures have improved, radiotherapy is used less frequently, and biopsy for brainstem LGGs is rarely performed.

To assess the effects of these changing practices on patient survival, Mayo Clinic researchers conducted two retrospective studies of long-term survival in children with LGGs. The first, one of the largest such studies undertaken, examined prognostic factors and survival patterns over the past 40 years. Results were published in the April 2013 issue of Journal of Pediatric Hematology/Oncology. The second evaluated outcomes and long-term survival in pediatric brainstem LGGs.

Prognosis and survival in LGGs

The Mayo Clinic team reviewed the records of 351 pediatric patients who had a diagnosis of LGG at Mayo Clinic in Rochester, Minn., and divided them into two groups:

  • Those with the initial diagnosis from 1970 to 1989 (group I)
  • Those with the initial diagnosis from 1990 to 2009 (group II)

Prognostic factors were recorded and analyzed statistically to determine their association with overall survival and progression-free survival. The results showed some improvement in both overall and progression-free survival rates:

  • Ten-year survival rates for groups I and II were 86.9 percent and 94.4 percent, respectively
  • Ten-year progression-free survival rates for groups I and II were 57.4 percent and 67.7 percent, respectively

In both groups, the most important factor associated with improved survival was gross total resection, with an overall progression-free survival rate at 10 years of 71.3 percent. Gross total resection was achieved more often in group II than in group I.

"With advances in imaging and surgical techniques, the number of patients with complete resection is increasing, and they are surviving longer. This study confirms the importance of aggressive surgery to give patients the best survival rates possible," says Nadia N. Laack, M.D., a radiation oncologist at Mayo Clinic in Rochester, Minn., and lead investigator of the study.

Importantly, the Mayo study found that when gross total resection was not achieved, survival rates improved with postoperative radiotherapy. In group II, the 10-year progression-free survival rate was 32.0 percent after subtotal resection without radiotherapy but was 75.7 percent with radiotherapy — similar to the 10-year progression-free survival rate for patients who have total resection (71.3 percent).

"The good news is that for the small group of patients in whom total resection is not possible, radiation therapy reduces the chance of recurrence to about the same level as in patients with complete resection," Dr. Laack says.

The Mayo study documented a sharp decline in the number of patients receiving postoperative radiation therapy for pediatric LGGs: 36.2 percent of patients in group I vs. just 9.6 percent in group II. Dr. Laack suggests the decline is due not only to an increase in gross total resections, thus reducing the need for postoperative radiation therapy, but also to concerns about the effects of radiation on the developing brain.

"There are definite cognitive and vascular risks associated with radiation therapy in children," Dr. Laack says. "The highest risks are for children under 5 years of age. The risks decrease every year, and above age 12 years, they decrease significantly."

More research is needed to help determine optimal treatment for pediatric LGGs. For clinicians, it is a delicate balancing act. "We can follow the tumor on MRI and do two or three surgeries over time if necessary to delay irradiation until the brain has developed further," says Nicholas M. Wetjen, M.D., a pediatric neurosurgeon at Mayo Clinic in Minnesota and co-author of the study. "But knowing when to do another surgery and when to start irradiation remains a challenge."

Histology and survival in brainstem LGGs

The prognosis for children with brainstem LGGs is generally considered poor, regardless of the tumor classification. Diagnosis often relies on MRI to avoid damaging the brainstem with biopsy. However, in the era before MRI, brainstem gliomas were frequently biopsied.

To learn more about the role of histologic grade and tumor location in childhood brainstem tumors, Drs. Laack and Wetjen and their colleagues studied the records of 48 children with biopsy-proven brainstem LGGs. The patients were treated at Mayo Clinic in Minnesota from 1971 to 2004 and monitored until the time of analysis in March 2011.

The results confirmed those in previous studies, indicating differences in survival depending on tumor location. But the Mayo study also uncovered differences in outcome depending on the tumor grade. Overall survival rates at five years were:

  • A rate of 85.7 percent for intrinsic focal grade I tumors vs. 66.7 percent for grade II
  • A rate of 77.7 percent for cervicomedullary grade I tumors vs. 50 percent for grade II

Diffuse pontine glioma (DPG) is highly aggressive and rarely biopsied. However, the Mayo study included 13 patients with DPG classified as grade I or grade II on biopsy. The median survival for patients with low-grade DPG was 1.8 years, in contrast to less than one year for DPG patients in previous studies. Four of the patients with low-grade DPG in the Mayo study had survival that exceeded five years.

"Not all brainstem tumors are high grade; there is significant variation," Dr. Laack says. "Our findings suggest a role for biopsy in brainstem tumors. Understanding the histology of these tumors is important because we now have different chemotherapies and radiation therapies for low- and high-grade tumors."

Dr. Wetjen adds: "Biopsy is not as risky as it was 20 years ago. We have much better image guidance now."

At Mayo, retrospective studies of clinical practices are a key focus of research. "We have a long history of trying to learn from the past in order to advance science for the future," Dr. Laack notes. "As practices change, our goal is to determine what's best for the patient."

For more information

Youland RS, et al. Prognostic factors and survival patterns in pediatric low-grade gliomas over 4 decades. Journal of Pediatric Hematology/Oncology. 2013;35:197.