Diffuse midline gliomas in children: Does changing strategies change results?
Authors: Kebudi Rejin , Yildirim Ulku Miray Miray , Iribas Ayca , Yaman Agaoglu Fulya , Zulfikar Osman Bulent 
Published: June 2024

10045

Background: The prognosis of children with diffuse intrinsic pontine gliomas (DIPG)/diffuse midline glioma (DMG) is dismal. Radiotherapy (RT) is considered the standard of treatment. We previously published results of our center, where patients receiving temozolomide or other chemotherapy after radiotherapy (RT) had a better survival than those receiving RT alone (1). This study aims to evaluate a larger cohort of children with DMG in a single center. Methods: We retrospectively reviewed demographic, clinical characteristics and treatment outcome of children with DMG diagnosed and treated at Istanbul University, Oncology Institute between Feb1999-Feb 2023. We compared the groups that received only radiotherapy (Group 1, only RT, n=19), the ones that received RT with concomitant and adjuvant temozolomide po (Group 2-n= 38 TMZ 75 mg/m2/day for 6 weeks concomitant (c.) with RT, followed by TMZ (200 mg/m2/day) for 5 days every 28 days until progression or for 12 cycles), and the ones that received RT with c. TMZ, followed by other systemic agents (Group 3 n= 18 RT c.TMZ, followed by nimotuzumab containing regimens; Group 4 the rest 26 received other agents such as bevacizumab, CCNU, ONC201 and other). The ones that progressed on group 2, received nimotuzumab containing or other regimens. Results: 114 children (49 female, 65 male) with a mean age of 7± 4 years (6 months-16 years) were analyzed. The most frequent clinical findings were ataxia, strabismus and motor weakness. 108 had diffuse intrinsic pontine gliomas (DIPG). In total 106 patients received RT, 54-60 Gy to the tumor site. The overall survival (OS) in all patients at 2 years, 3 years and 5 years were 25.6%,15% and 11.5% respectively. The 2 years, 3 years and 5 years OS in group1 were 0.79%, 0% ,0% respectively; in group 2 they were 38.4%, 27.9%, 16%respectively ; in group 3 they were 17.6% , 0 % ,0% respectively, in Group 4 they were 10.3%, 0.34%, 0% respectively, The OS in Group 2 or3 or 4 were significantly higher than group 1 (only RT) (P =0.002, p=0.004, p<0.001,respectively). There was no major side effect due to TMZ, nor nimotuzumab. Seven patients were re-irradiated at progression. The number of patients undergoing biopsies and molecular testing increased to 50% of the patients after 2016 versus only in two patients previously. Conclusions: In our series, the overall survival was significantly superior in patients who received RT with concurrent and adjuvant temozolomide and/or adjuvant nimotuzumab containing regimens or other adjuvant systemic treatment in comparison to patients that received RT alone, suggesting that adding systemic treatment after RT (poTMZ or iv nimotuzumab containing regimens or other) may help extend survival. Oral temozolomide may be easier to use as first line treatment after radiotherapy especially in resource limited settings, switching to nimotuzumab containing or other chemotherapy and/or re-radiotherapy at progression. 1. Kebudi R, 2013.