2019-08-012024-05-18https://scholars.lib.ntu.edu.tw/handle/123456789/702672摘要：臨床需求 神經膠母細胞瘤治療後，中位存活期約14個月，五年無復發率<5%。雖多為局部復發，但受限腦組織耐受度，無法提高局部放射線劑量。 應對策略 以局部藥物傳輸系統搭載放射線增敏抗癌藥，協同減劑量放射線強化抗癌效應並降低腦損傷。 目前成果 本團隊分析病人磁振造影，找出預測侷限型腫瘤 (局部復發) 之影像生物標記。以此影像分析模式進行台日合作研究，發現侷限型病人接受局部高劑量質子放射治療，五年無復發率38%。顯示強化局部治療策略，可有效提高侷限型病人腫瘤控制。為提升放射線抗癌效果，本團隊整合材料科學研發「局部藥物傳輸系統搭載放射線增敏抗癌藥」策略已證實「腫瘤內注射水膠搭載卡鉑合併放射治療」動物模型之可行性與協同效應。 進階計畫 (本計畫) 為達臨床應用目標，提出局部藥物傳輸系統進階研發計畫。材料科學方面，以水膠與碳酸鈣複合物為卡鉑藥物載體，利用水膠熱塑、順形與緩釋性，以及癌細胞周邊為酸性環境，可使碳酸鈣分解釋放藥物進入癌細胞，提升藥物在癌細胞停留時間與抗癌效果。以細胞與小鼠模型驗證局部藥物傳輸協同減劑量放射線之抗癌效應與腦組織耐受度。 預期結果 局部藥物傳輸系統研發搭配放射線策略，可望優化神經膠母細胞瘤精準化治療成效。<br> Abstract: Unmet clinical need For glioblastomas, the median overall survival (OS) and 5-year complete response (CR) rate after treatment are around 14 months and <5%, respectively. Most tumor recurrence is local; however, the local radiotherapy dose delivery is limited by the brain tissue tolerance. Corresponding treatment strategy To satisfy the unmet clinical need, we combined local delivery of radiosensitizer and reduced-dose radiation to enhance the anticancer effect as well as to reduce the radiation brain damage. Present results Through analyzing patient’s MRI scan, we established the imaging biomarkers to classify restrictive type glioblastoma, i.e. those with the tendency of local recurrence. In our Taiwan-Japan collaboration research, utilizing the imaging analysis method, the median OS and 5-year CR rate for restrictive type glioblastoma receiving high-dose proton therapy were 77 months and 38%, respectively, which suggests locally intensive radiotherapy increases the tumor control. To enhance the anticancer effect of radiotherapy, we integrated the material science to develop the local delivery system of radiosensitizer and anticancer drug. The feasibility and synergistic effect of combined intratumoral injection of hydrogel carboplatin with radiation were successfully demonstrated using the mouse model. Advanced project To facilitate the further clinical application, herein, we propose the original advanced local drug delivery system, which intends combine hydrogel and CaCO3 to carry carboplatin. The thermal gelling and conformal features of hydrogel help the sustained release of carboplatin. Furthermore, the carboplatin-loaded CaCO3 decomposes and releases carboplatin in the acidic environment of cancer cells, which assists carboplatin stay in cancer cells to enhance the damage to cancer cells. We hypothesize that the synergistic effect of local delivery of carboplatin enables the reduced-dose radiation to eradicate cancer cells. The purpose of this research project is to verify our hypothesis by demonstrating the anti-cancer effect of combined the local drug delivery and reduced-dose radiation through the comprehensive cell and mouse experiment design. Expected results The strategy of combine local drug delivery system with radiation is potential to optimize the personalized glioblastoma treatment effect.放射治療惡性膠質瘤同步放化療局部藥物注射個人化治療Radiotherapymalignant gliomaconcurrent chemoradiotherapylocal drug deliverypersonalized treatment