The importance of total dose intensity in the treatment of primary central nervous system lymphoma

Abstract

13004 Background: Chemotherapy effectiveness in treating malignant brain tumors (e.g. primary central nervous system lymphoma or PCNSL) is thought to improve as total dose intensity delivered to the tumor increases. This report assesses the impact of total dose intensity in a large case series of newly-diagnosed PCNSL patients. Methods: A previously-reported series of 149 PCNSL patients treated at four centers (Angelov et al, JCO 25:18S, 2007, abstract 2014) treated with a methotrexate-based regimen in conjunction with blood- brain barrier disruption (BBBD), without up-front whole brain radiotherapy was analyzed. The degree of disruption was recorded for each BBBD procedure. ECOG performance status, number of disruptions, and a cumulative degree-of-disruption score were used as time-dependent covariates in proportional hazards regression models (adjusted for potential confounders) to predict survival. Results: Mean number of disruptions was 14.0 (SD 7.8) and mean cumulative degree of disruption score was 44.3 (SD 27.5). Number of disruptions (hazard ratio 0.911, 95% CI: 0.880, 0.944) and cumulative degree of disruption score (hazard ratio 0.974, 95% CI: 0.964, 0.983) were significant predictors of survival. Controlling for age and performance status (at baseline value and as a time-dependent covariate) did not substantially change the hazard estimate or its p-value. Conclusions: These results support a dose response relationship between dose intensity and survival, in patients with PCNSL. Use of these predictors as time-dependent covariates avoids a survival bias that could otherwise result. Conclusion: There is a statistically significant association between total dose intensity and survival in these patients supporting the efficacy and importance of blood-brain barrier disruption for treating PCNSL patients. No significant financial relationships to disclose.