利用葡萄糖正子掃描評估早期治療反應來預測轉移性肺腺癌病患接受得紓緩標靶藥物之預後

Abstract

目的: 本研究在探討利用葡萄糖正子掃描評估轉移性肺腺癌接受得紓緩標靶藥物治療之早期反應，以TLG-S方法是否比EORTC標準與PERCIST標準更能有效預測病患之預後。此研究的假設是源自於原發腫瘤與轉移腫瘤的生物特性差異以及骨骼顯像上的復燃現象。此外，腫瘤影像上的紋理特性對於疾病預後的價值也進行探討。 方法: 我們回溯性分析前瞻性收集的23位接受得紓緩治療之轉移性肺腺癌病患。每位受試者都接受葡萄糖正子掃描於給藥前，給藥第14日，與給藥第56日。診斷性電腦斷層於給藥前與給藥第56日施行。葡萄糖正子掃描的反應評估利用TLG-S、EORTC與PERCIST標準進行。 電腦斷層的RECIST 1.1標準作為治療反應的比較基準。影像紋理特性分析了coarseness、contrast、busyness、complexity與strength參數。兩年無惡化存活期與整體存活期作為疾病預後的評估指標。 結果: 我們發現13位病患有骨骼轉移。其中4位(31%)在給藥第14日有發生骨骼顯像上的復燃現象，依據PERCIST標準被誤判為藥物不反應組。依據給藥第14日TLG-S標準被歸為藥物有反應組之病患，擁有較高的兩年無惡化存活期(26.7% vs. 0%, P = 0.007) 與整體存活期(40.0% vs. 7.7%, P = 0.018)。依據給藥第56日電腦斷層RECIST 標準也呈現相同的存活期。依據給藥第14日EORTC標準被歸為藥物有反應組之病患，擁有較高的兩年整體存活期(36.4% vs. 8.3%, P = 0.015)。早期busyness參數的變化在無惡化存活期有顯著意義(P = 0.004) 且早期coarseness參數的變化在無惡化存活期(P = 0.007)及整體存活期(P = 0.037) 有顯著意義。參數busyness與coarseness變化與腫瘤體積變化呈現相關性(r = 0.835 and r = -0.368)。 結論: 利用PERCIST標準評估轉移性肺腺癌接受得紓緩治療反應時，骨骼顯像上的復燃現象可能會影響判讀。此時，TLG-S標準用於評估病患預後可能有較佳的幫助。對於影像紋理特性在疾病預後的解讀必須謹慎。

Abstract Purpose: In this prospective study, we sought to investigate whether early FDG-PET assessment of treatment response using total lesion glycolysis measured with a systemic approach (TLG-S) could be superior to either local assessment with EORTC (European Organization for Research and Treatment of Cancer) criteria or single-lesion assessment with PERCIST (PET Response Criteria in Solid Tumors) for predicting clinical outcomes in patients with metastatic lung adenocarcinoma treated with erlotinib. The study hypothesis originated from the potential occurrence of the flare phenomenon and the differences in tumor biology between primary malignant cells and their metastasized progenies. In addition, the prognostic value of tumor textural features was investigated. Methods: We performed a retrospective review of prospectively collected data from 23 patients with metastatic lung adenocarcinoma treated with erlotinib. All participants underwent FDG-PET imaging at baseline and on days 14 and 56 after completion of erlotinib treatment. In addition, CT scans were performed at baseline and on day 56. FDG-PET response was assessed with TLG-S, EORTC, and PERCIST criteria. Response assessment based on RECIST 1.1 (Response Evaluation Criteria in Solid Tumors) from CT imaging was used as the reference standard. Regional textural features were analyzed using neighborhood grey-tone difference matrix with parameters of coarseness, contrast, busyness, complexity, and strength. Two-year progression-free survival (PFS) and overall survival (OS) served as the main outcome measures. Results: We identified 13 patients with bone metastases. Of them, four (31%) had bone flares at day 14 and were erroneously classified as non-responders according to the PERCIST criteria. Patients who were classified as responders on day 14 based on TLG-S criteria had higher 2-year PFS (26.7% vs. 0%, P = 0.007) and OS (40.0% vs. 7.7%, P = 0.018) rates. Similar rates were observed in patients who responded on day 56 according to the RECIST criteria based on CT imaging. Patients classified as responders on day 14 according to the EORTC criteria on FDG-PET imaging had a better 2-year OS rate compared with non-responders (36.4% vs. 8.3%, P = 0.015). The early change of busyness showed significantly better PFS (P = 0.004) and the coarseness change demonstrated significantly better outcomes in PFS (P = 0.007) and OS (P = 0.037). The busyness and coarseness changes were correlated with tumor volume changes (r = 0.835 and r = -0.368). Conclusions: Bone flares that can interfere with the interpretation of treatment response according to the PERCIST criteria are not uncommon in patients with metastatic lung adenocarcinoma treated with erlotinib. In this scenario, TLG-S criteria may help to better predict survival outcomes than other forms of assessment. Interpretation of textural features for prognosis should be cautious.