Early Therapeutic Interventions for Newly Diagnosed Glioblastoma: Rationale and Review of the Literature

Glioblastoma is the commonest primary brain cancer in adults whose outcomes are amongst the worst of any cancer. The current treatment pathway comprises surgery and postoperative chemoradiotherapy though unresectable diffusely infiltrative tumour cells remain untreated for several weeks post-diagnosis. Intratumoural heterogeneity combined with increased hypoxia in the postoperative tumour microenvironment potentially decreases the efficacy of adjuvant interventions and fails to prevent early postoperative regrowth, called rapid early progression (REP). In this review, we discuss the clinical implications and biological foundations of post-surgery REP. Subsequently, clinical interventions potentially targeting this phenomenon are reviewed systematically.

Early interventions include early systemic chemotherapy, neoadjuvant immunotherapy, local therapies delivered during surgery (including Gliadel wafers, nanoparticles and stem cell therapy) and several radiotherapy techniques. We critically appraise and compare these strategies in terms of their efficacy, toxicity, challenges and potential to prolong survival. Finally, we discuss the most promising strategies that could benefit future glioblastoma patients. There is biological rationale to suggest that early interventions could improve the outcome of glioblastoma patients and they should be investigated in future trials.