Role of Surgery in the Treatment of Pediatric Low-grade Glioma with Various Degrees of Brain Stem Involvement

Objective: Posterior fossa pediatric low-grade glioma involving the brainstem and cerebellar peduncles (BS-pLGG) are a subgroup with higher risks at surgery. We retrospectively analyzed the role of surgery in the interdisciplinary armamentarium of treatment options in our institutional series of BS-pLGG with various degrees of brainstem involvement.

Material And Methods: We analyzed data of 52 children with BS-pLGG after surgical intervention for clinical/molecular characteristics, neurological outcome, factors influencing recurrence/progression pattern, and tumor volumetric analysis of exclusively surgically treated patients to calculate tumor growth velocity (TGV). Tumors were stratified according to primary tumor origin in four groups: (1) cerebellar peduncle, (2) 4th ventricle, (3) pons, (4) medulla oblongata.

Results: The mean FU was 6.44 years. Overall survival was 98%. The mean PFS was 34.07 months. Two patients had biopsies only. Fifty-two percent of patients underwent remission or remained in stable disease (SD) after initial surgery. Patients with progression underwent further 23 resections, 15 chemotherapies, 4 targeted treatments, and 2 proton radiations. TGV decreased after the 2nd surgery compared to TGV after the 1st surgery (p < 0.05). The resection rates were significantly higher in Groups 1 and 2 and lowest in medulla oblongata tumors (Group 4) (p < 0.05). More extended resections were achieved in tumors with KIAA1549::BRAF fusion (p = 0.021), which mostly occurred in favorable locations (Groups 1 and 2). Thirty-one patients showed postoperatively new neurological deficits. A total of 27/31 improved within 12 months. At the end of FU, 6% had moderate deficits, 52% had mild deficits not affecting activities, and 36% had none. Fifty percent of patients were free of disease or showed remission, 38% were in SD, and 10% showed progression.

Conclusion: The first surgical intervention in BS-pLGG can control disease alone in overall 50% of cases, with rates differing greatly according to location (Groups 1 > 2 > 3 > 4), with acceptable low morbidity. The second look surgery is warranted except in medullary tumors. With multimodality treatments almost 90% of patients can obtain remission or stable disease after > 5 years of follow-up. An integrated multimodal and multidisciplinary approach aiming at minimal safe residual disease, combining surgery, chemo-, targeted therapy, and, as an exception, radiation therapy, is mandatory.