2612 - Histone-Altered Diffuse Midline Glioma (DMG): Clinic-Pathological Spectrums and Outcomes from a Large Specialized Neuro-Oncology Practice in India

08:00am - 09:00am PT

Hall F

Screen: 16

POSTER

Presenter(s)

Meenakshi Jeeva, MD - Princess Margaret Cancer Center, University Health Network, Toronto, ON

M. Jeeva¹, M. Gurav², A. Chatterjee¹, O. Shetty², P. Gogte², A. Dasgupta¹, G. Chinnaswamy³, M. Prasad³, A. Moiyadi⁴, P. Shetty⁴, A. Sahay², A. Shah², A. Sahu⁵, A. K. Choudhari⁵, K. Bhattacharya⁵, E. Sridhar², and T. Gupta¹; ¹Department of Radiation Oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, India, ²Department of Pathology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, India, ³Department of Pediatric Oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, India, ⁴Department of Neurosurgery, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, India, ⁵Department of Radio-diagnosis, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, India

Purpose/Objective(s): Histone-altered DMGs are rare and lethal tumors that primarily affect children and young adults and are best treated within the framework of a multidisciplinary neuro-oncology practice. We summarize herein a decade-long experience with H3K27M-altered DMGs treated at a comprehensive cancer center in India

Materials/Methods: Patients with biopsy-proven H3K27M-mutant DMGs were identified from prospectively maintained clinical neuro-oncology and neuropathology databases. Clinico-demographic characteristics, histo-molecular features, treatment details, and survival outcomes were retrospectively retrieved from institutional records. All patients underwent either biopsy or safe debulking surgery, followed by radiotherapy (RT) in those with good performance status. Concurrent and adjuvant Temozolomide (TMZ) were administered on a case-to-case basis. Progression-free survival (PFS) and overall survival (OS) were calculated using Kaplan-Meier methods and expressed as point estimates with 95% confidence intervals (CIs). Time to leptomeningeal dissemination (LMD) was assessed as an outcome of secondary interest.

Results: Demographic and pathology diagnostics data were available for the entire cohort (228 patients) whereas treatment and outcomes data was restricted to 197 patients. The median age at diagnosis was 20 years (IQR: 11-30 years) with 70% being =12 years of age. Tumors were midline and predominantly supratentorial (80%). The majority (77%) received some form of RT. At a median follow-up of 12 months (95%CI: 9.83- 13.48 months), 1-year PFS and OS were 31% (95% CI: 25-37%) and 48% (95%CI: 41-55%), respectively, with median PFS and OS of 17 (95%CI: 6-10 months) and 12 months (95%CI: 10-14 months). Multivariate analysis identified extent of resection (EOR) (p=0.03), receipt of RT (p=0.002), and addition of TMZ (p=0.03) as independent prognostic factors for OS. The EOR (p=0.04) and addition of TMZ (p=0.02) were found to be associated with improved PFS. Dissemination was seen in 10.5% patients at baseline and 23.5% at relapse. The Median time to LMD from diagnosis was 7.7 months (IQR: 4-10 months). The median OS for patients with LMD at diagnosis and progression were 9 months (IQR: 4-18 months) and 5 months (IQR: 3-9 months) respectively. Twelve patients (predominantly adults) were long-term survivors at more than 5-years from diagnosis.

Conclusion: H3K27M-altered DMG is an aggressive CNS tumor, primarily affecting children and young adults. Improvement in survival can be achieved with the addition of RT and TMZ. Larger collaborative studies are needed to further improve outcomes.