Feifei Teng1, Christina I Tsien2, Theodore S Lawrence3, Yue Cao4. 1. Department of Radiation Oncology, Ann Arbor, United States; Department of Radiation Oncology, Shandong Cancer Hospital, Shandong University, Jinan, China. 2. Department of Radiation Oncology, Washington University, St. Louis, United States. 3. Department of Radiation Oncology, Ann Arbor, United States. 4. Department of Radiation Oncology, Ann Arbor, United States; Department of Radiology, Ann Arbor, United States; Department of Biomedical Engineering, University of Michigan, Ann Arbor, United States. Electronic address: yuecao@umich.edu.
Abstract
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 (Ktrans), 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 Ktrans>0.005min-1 (%Vall) less or greater than 50%. Time-course changes of %Vall 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), %Vall 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), %Vall 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.
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 (Ktrans), 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 Ktrans>0.005min-1 (%Vall) less or greater than 50%. Time-course changes of %Vall 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), %Vall 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), %Vall 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.
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