Defining rapid early progression in glioblastoma-A volumetric approach

The current treatment of glioblastoma involves resection followed by radiotherapy (RT) and temozolomide. Rapid early progression (REP) of tumor in the surgery-to-radiotherapy interval (SRI) has been described using categorical or semi-quantitative assessments and is associated with inferior clinical outcomes. This study seeks to establish and validate a quantitative definition for REP and examine how REP could inform future therapy.

Volumes of tumor and resection cavity at 3 time points-preoperative, postoperative and RT-planning (pre-RT)-were contoured among patients who had undergone standard of care. A minimal, but clinically appreciable, threshold for defining REP based on change in tumor volume was established, validated, and subsequently used to assess actionable predictors of REP and its prognostic value.

An increase of >2 cc in volume or a new satellite tumor between the post-operative to planning MRI was found to be a sensitive, pragmatic, and statistically significant cutoff for REP (P = .002). Actionable predictors such as SRI of 6 weeks and a > 5 cc residual immediate post-operative tumor volume were found to be statistically significant predictors of REP. REP was also found to be a statistically significant prognostic indicator for overall survival (P = .002) and progression-free survival.

These findings support that an increase in tumor volume between post-operative and pre-RT MRI of >2 cc is the ideal working definition of REP in this clinical setting. Furthermore, REP could serve as a prognostic -biomarker to track treatment response. Additionally, 2 actionable predictors of REP, post-op residual tumor volume and SRI, are identified.