Aim: To assess systemic inflammatory biomarkers in non invasive differential diagnosis of primary central nervous system lymphoma (PCNSL) from high-grade glioma (HGG). Materials & methods: Patients with similar morphology (PCNSL or HGG) on conventional neuro-imaging were included. Systemic inflammatory indices were calculated from pretreatment complete blood counts and liver function tests and compared against histopathology as reference standard. Results: Mean values of absolute lymphocyte count and prognostic nutritional index were significantly different between PCNSL (n = 42) versus HGG (n = 16). Area under receiver operating characteristics curve for absolute lymphocyte count and prognostic nutritional index in the diagnosis of PCNSL was 0.70 and 0.72 respectively suggesting fair and acceptable diagnostic accuracy. Conclusion: Systemic inflammatory biomarkers complement established clinico-radiological features and aid in the differential diagnosis of PCNSL from HGG.

BACKGROUND Adult diffuse high-grade gliomas (HGG) predominantly recur locally despite adequate treatment. At recurrence, salvage chemo-reirradiation (CTRT) provides durable local control with significant risk of symptomatic radionecrosis (RN). Reirradiation (reRT) is delivered using either conventional fractionation (CFRT) or hypofractionation based on institutional preferences. Studies have shown that the addition of bevacizumab, a monoclonal antibody inhibiting vascular endothelial growth factor to reRT reduces the risk of RN and potentially improves survival, providing strong scientific rationale for the combination. OBJECTIVE Primary endpoint would be a composite endpoint of 1-year event-free survival (EFS) comprising recurrence, symptomatic RN or death as an event. Secondary endpoints include progression-free survival, cumulative incidence of symptomatic RN, and overall survival. Quality-of-life assessment and health-economics would be tertiary endpoints. METHODS Target population includes adults with local recurrence (radiology and/or histology) of biopsy-proven diffuse HGG >2-years from primary RT. This is an open-label, phase III randomised control trial using a 2 x 2 factorial design comparing the addition of bevacizumab to chemo-reirradiation (test arm) versus chemo-reirradiation alone (control arm) using a superiority hypothesis. Patients in test arm will receive 6 months of bevacizumab (5mg/kg) 2 weekly, along with standard 6 cycles of temozolomide, starting 1 month following reRT completion. All patients will be further randomized to CFRT (50.4-55.8Gy/28-31/5.5-6 weeks) as control arm versus moderately HFRT (35Gy/10 fractions/2 weeks) as test arm in 1:1 ratio using a non-inferiority hypothesis. The desired sample size is 257 (two-sided alpha 0.05, power 80%, and 10% attrition rate) with a superiority hypothesis of 1-year EFS 45% (bevacizumab with CTRT) vs 30% (CTRT), and non-inferiority hypothesis of 25% (HFRT) vs 37% (CFRT),with delta of 12%. DISCUSSION The study will answer critical questions regarding the role of bevacizumab in recurrent HGG along with reRT, along with the differences in outcomes using normofractionated or hypofractionated RT.