磁振正子掃描於非小細胞肺癌放射線治療療效評估之應用

Application of MR-PET in radiotherapy treatment response evaluation of non-small cell lung cancer

黃昱森(Yu-Sen Huang)

指導教授 ： 趙福杉

國立臺灣大學/工學院/醫學工程學研究所/博士(2017年)

https://doi.org/10.6342/NTU201800096

摘要

肺癌近幾年居國人十大癌症死因排行榜的第一位。非小細胞肺癌約佔所有肺癌病人數之85%以上。身體立體定位放射治療為無法開刀的早期肺癌病人之首選治療，而治癒性化學放射治療則為局部晚期肺癌病人之標準治療。目前尚無準確的影像學方法可於治療初期優先預測腫瘤治療後之反應。整合型磁振正子掃描是一種新型影像技術，可早期評估腫瘤對於放射治療的反應，希望能儘早預測疾病進展和病人存活。
在本研究的第一部分，我們前瞻性納入了17例接受身體立體定位放射治療的非轉移性非小細胞肺癌早期患者。我們分析正子掃描之標準攝取值，核磁共振之動態顯影掃描影像參數，及擴散加權影像參數，包括：腫瘤大小、SUV、ADC、Ktrans、kep、ve、vp及iAUC60。結果顯示，整合型磁振正子掃描可測量身體立體定位放射治療後之腫瘤參數變化，如SUVmax（p <0.001）、Ktrans平均值（p = 0.005）、Ktrans標準差（p = 0.046）、kep平均值（p = 0.014）、kep 標準差（p = 0.001）和vp 標準差（p = 0.002）。正子掃描相關參數SUVmax與磁振掃描相關參數kep平均值（p = 0.002）和kep 標準差（p < 0.001）呈顯著線性相關。在身體立體定位放射治療後6週，Ktrans平均值下降之百分比（p < 0.001）及kep平均值下降之百分比（p = 0.034），此兩者皆與腫瘤大小縮小之百分比呈顯著線性相關。
在本研究的第二部分，我們前瞻性納入17例接受治癒性化學放射治療的非轉移性非小細胞肺癌局部晚期患者。結果顯示，整合型磁振正子掃描可測量化學放射治療後之腫瘤參數變化，如SUVmax（p <0.001）、Ktrans平均值（p = 0.004)、Ktrans標準差（p = 0.022）、kep平均值（p = 0.016)、kep 標準差（p = 0.018）、vp標準差（p < 0.001）和iAUC60（p = 0.014）。化學放射治療後SUVmax仍大於10的病人，肺癌局部復發之風險較高（p <0.001)，且總體生存期較短（p = 0.006）。在回歸分析中，化學放射治療後SUVmax小於5、Ktrans降低且ADC增加的病人，對治療效果較好，腫瘤局部復發或遠端轉移之風險較低 (Hazard ratio: 1.0)，化學放射治療後SUVmax仍大於5且Ktrans增加的病人，對治療效果差，腫瘤局部復發或遠端轉移之風險高 (Hazard ratio: 11.5)。
根據上述結果，我們證明了此新型影像技術精準結合了正子掃描及核磁共振之優點，在同一次檢查中即可對腫瘤進行深入評估；整合型磁振正子掃描確實可以早期評估腫瘤對於放射治療的反應，並可有效預測局部治療反應、疾病進展及病人存活。

關鍵字

磁振正子掃描 ； 動態顯影 ； 非小細胞肺癌 ； 放射線治療 ； 療效評估

並列摘要

Dynamic contrast-enhanced (DCE) integrated magnetic resonance positron emission tomography (MR-PET) is a novel image technique for earlier evaluation of tumor response to radiotherapy, leading to earlier predicting disease progression and patients’ survival. Stereotactic body radiotherapy (SBRT) is a standard treatment option for patients with stage I non-small cell lung cancer (NSCLC), and chemoradiotherapy (CRT) is the treatment of choice for patients with unresectable or locally advanced stage III NSCLC.
In the first part of the study, we prospectively enrolled 19 lung tumors in 17 non-metastatic NSCLC patients who were receiving SBRT as a primary treatment. They underwent DCE-integrated MR-PET before and 6 weeks after SBRT. The following image parameters were analysed: tumor size, standardized uptake value (SUV), apparent diffusion coefficient, Ktrans, kep, ve, vp, and iAUC60. Chest computed tomography (CT) was performed at 3 months after SBRT. The results showed that SBRT treatment led to a functional change in the tumor, as demonstrated by significant decreases in the SUVmax (p<0.001), Ktrans mean (p=0.005), Ktrans standard deviation (SD; p=0.046), kep mean (p= 0.014), kep SD values (p=0.001), and vp SD (p=0.002). The PET functional value SUVmax was correlated with the MR functional values kep mean (p=0.002) and kep SD (p<0.001). The percentage reduction in Ktrans mean (p<0.001) and kep mean ( p=0.034) at 6 weeks post-SBRT were significantly correlated with the percentage reduction in tumor size, as measured using CT at 3 months after SBRT. Univariate analyses revealed a trend toward disease progression when the initial SUVmax > 10 (p=0.083).
In the second part of the study, we prospectively enrolled 17 non-metastatic NSCLC patients receiving CRT as primary treatment. The results showed that CRT led to tumor significant decreases in SUVmax (p < 0.001), Ktrans mean and standard deviation (SD, p = 0.004 and 0.022, respectively), kep mean and SD (p = 0.016 and 0.018, respectively), vp SD (p < 0.001), and iAUC60 (p = 0.014). The median follow-up time was 12.0 months. Patients with post-CRT SUVmax > 10 were prone to local failures and poor overall survival (p < 0.001 and p = 0.006, respectively). In proportional hazards regression analyses via the stratified Cox model, we identified post-CRT SUVmax >5 and increasing Ktrans as predictor of local failure and distant metastasis (Hazard ratio: 11.5), as well as poor patient survival.
In conclusions, DCE-integrated MR-PET imaging seems to be a promising addition to clinical examination and anatomic imaging for assessing the response of NSCLC to radiation therapy. This technology which combines PET and MRI facilitates the in-depth assessment of tumors in a single examination. In patients with NSCLC who are receiving radiation therapy, DCE-integrated MR-PET with parameters allows clinicians to evaluate the response early after radiation therapy, and to predict the local treatment response, disease progression, and survival.

並列關鍵字

MR-PET ； Dynamic contrast-enhanced ； Non-small cell lung cancer ； Radiotherapy ； Treatment response evaluation

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