Blood-tumor barrier opening changes in brain metastases from pre to one-month post radiation therapy

Purpose: Blood-tumor barrier is a limiting factor for effectiveness of systemic therapy to brain metastases. This study aimed to assess the extent and time course of BTB opening in BM following whole-brain radiotherapy (WBRT) or stereotactic radiosurgery (SRS) to determine optimal timing for systemic therapy.

Materials and method: 30 patients received WBRT or SRS and a total of 64 metastatic lesions were analyzed. Dynamic contrast-enhanced MRI were acquired, to quantify a transfer constant (K^trans), pre-RT, 1-2weeks after starting RT (Wk1-2), and 1-month post-RT (1M post-RT). Lesions were categorized as either low or high permeability based upon the pre-RT percentage volume of a lesion with K^trans>0.005min^-1 (%V_all) less or greater than 50%. Time-course changes of %V_all after RT were analyzed.

Results: Fifty-seven lesions had high-permeability and seven had low-permeability at baseline. Intra-patient and inter-lesion heterogeneity was observed in six patients who had both low- (n=7) and high-permeability lesions (n=10). Also, lesion permeability showed a significant size-effect at baseline. For high-permeability lesions, either received WBRT (n=43) or SRS (n=14), %V_all decreased non-significantly following RT (from 85.4% pre-RT to 76.9% 1M post-RT). For low-permeability lesions (n=7, all received WBRT), %V_all increased from 5.6% pre-RT to 30.2% at Wk1-2 and to 52.6% 1M-post (p=0.01).

Conclusion: Our preliminary results suggest that 2-4weeks after RT, when BTB opening is high for both low- and high-permeability brain metastatic lesions, could be optimal time to start systemic therapy.