ABSTRACT
Background: Contemporary standard-of-care for newly diagnosed glioblastoma (GBM) is maximal safe resection followed by postoperative focal conformal radiotherapy (RT) plus concurrent temozolomide (TMZ) and 6-cycles of adjuvant TMZ (Stupp regimen). However, many patients continue to receive extended adjuvant TMZ (beyond 6-cycles) without solid scientific evidence. This review pools data from nonrandomized studies and randomized controlled trials (RCTs) comparing extended adjuvant TMZ (>6-cycles) to standard adjuvant TMZ (6-cycles) in patients with newly diagnosed GBM for updated evidence-synthesis. Methods: This systematic review and meta-analysis was carried out in accordance with the Cochrane methodology including quality assessment of primary studies. Primary outcome of interest was comparative efficacy defined as progression-free survival (PFS) and overall survival (OS). Hazard ratios (HRs) for PFS and OS with corresponding 95% confidence interval (CIs) were extracted/computed from individual primary studies and pooled using random-effects model. Any p-value <0.05 was considered statistically significant. Results: Evidence-synthesis was based on pooling of data from 2578 patients enrolled in 16 nonrandomized comparative studies and 5 RCTs. Overall, extended adjuvant TMZ was associated with statistically significant reduction in the risk of progression (HR = 0.72, 95%CI: 0.60-0.87; p = 0.007) and death (HR = 0.71, 95%CI: 0.57-0.90; p = 0.004) compared to standard adjuvant TMZ. However, on subgroup analysis, survival benefit of extended adjuvant TMZ was limited to data synthesized from retrospective nonrandomized comparative studies with no statistically significant difference in outcomes seen after pooling of data from RCTs only. Conclusion: Apparent survival benefit of extended adjuvant TMZ in newly diagnosed GBM is largely driven by nonrandomized comparative studies with high inherent potential for multiple biases.
ABSTRACT
Primary diffuse leptomeningeal melanocytosis (PDLM) is an extremely rare CNS tumor with nonspecific clinicoradiologic features that overlap considerably with aseptic meningitis posing significant diagnostic and therapeutic challenges. We present one such case report of a patient treated empirically at first presentation as aseptic viral meningitis based on MRI and CSF analysis. Diagnosis of PDLM was established subsequently through meningeal biopsy that demonstrated a melanocytic tumor with fine granular melanin pigment without significant mitoses. Her systemic and ocular examination was unremarkable. Whole-body 18F-fluorodeoxyglucose PET/CT (FDG-PET/CT) did not identify any other primary site. Following ventriculoperitoneal shunt to relieve hydrocephalus, she was treated with definitive craniospinal irradiation plus whole-brain boost and remains stable on periodic clinicoradiologic surveillance. Optimal management of PDLM lacks consensus with role of radiotherapy, chemotherapy, targeted therapy and immunotherapy being controversial.
