在臨床期別T1aN0M0之非小細胞肺癌，淋巴腺轉移的預測因子

Predictive factors of lymph node metastasis in clinical T1aN0M0 non-small cell lung cancer

劉昭宇(Chao-Yu Liu)

指導教授 ： 陳晉興

國立臺灣大學/醫學院/臨床醫學研究所/碩士(2018年)

https://doi.org/10.6342/NTU201802633

摘要

背景
腫瘤體積較小的肺癌，在近年來有愈來愈多的病例因為電腦斷層篩檢的普即被早期發現。針對這些小的肺癌，肺局部切除手術已被許多文獻報告其療效相當於肺葉切除，包括病人術後的存活期。肺局部切除有保留病患肺功能的優點。然而在決定是否使用局部切除前，預測該病人的淋巴腺轉移狀態是一件非常重要的工作。在臨床分期T1N0M0的患者中，我們發現有一部分的病人，其預後特別差，通常跟手術後發現淋巴腺轉移(nodal upstaging)有關。因此能否在術前預測這群病人當中，什麼樣的患者其淋巴腺轉移的風險很高，是個重要的議題。在我們的研究中，我們的目標是要評估在肺腺癌腫瘤大小等於或小於兩公分的腫瘤中，淋巴節轉移的預測因子。

研究方法與材料
我們回溯性的蒐集自2011年1月至2015年12月在台大醫院接受肺癌手術的肺腺癌病患。我們特別要研究的預測因子為腫瘤大小、術前血清Carcinoembryonic antigen (CEA)值、電腦斷層影像上腫瘤毛玻璃部分佔整體腫瘤大小的比例。我們將用邏輯斯回歸方法來評估各項變數對淋巴腺轉移的預測價值。

結果
總共770位病患納入本次研究。14位(1.8%)為術後淋巴腺轉移(pN+)的患者。比較大的腫瘤大小，毛玻璃變化比例較少的，以及較高的血清CEA值是術後淋巴腺轉移的顯著預測因子。從腫瘤的組織病理亞型來看，較少lepidic的部份，有臟層肺膜的侵犯、和有淋巴血管的侵犯也跟淋巴腺轉移有密切的相關。若將術前的連續變項因子改為類別因子，我們可得到腫瘤大小≥ 1.5 cm 、血清CEA值≥ 3 ng/mL、和毛玻璃變化佔腫瘤比例< 25%有顯著的淋巴腺轉移的預測價值。

結論
在臨床分期為T1aN0M0 (腫瘤≦2公分)的非小細胞肺癌患者中，腫瘤大小、術前血清CEA值、以及電腦斷層影像毛玻璃變化(GGO)所佔的比例，是為預測術後淋巴腺是否轉移的顯著的預測因子。臨床實務上，若腫瘤< 1.5 公分，電腦斷層影像上腫瘤呈現以GGO為主的影像型態，並且患者術前血清CEA < 3 ng/mL，可以選擇性地避免進行根除性淋巴結廓清，作為手術治療的策略。

關鍵字

非小細胞肺癌 ； 淋巴腺轉移 ； 毛玻璃變化 ； 肺局部切除 ； 預測因子

並列摘要

Introduction
Lung cancer with small tumor size is now frequently being detected because of the prevalent use of computed tomography (CT) as a screening tool for pulmonary lesions. Sublobar resections (wedge resection/ segmentectomy) for small non-small cell lung cancer (NSCLC) have been reported to be non-inferior to lobectomy with regard to the surgical outcomes. However, a small group of cT1N0M0 NSCLCs tend to have a worse prognosis than expected, and nodal upstaging after surgery is the main reason. Prediction of pathologic nodal upstaging is important. In our study, we aimed to reappraise the predictive factors of lymph node metastases in cT1aN0M0 (AJCC 7th edition for lung cancer) NSCLC.
Methods
Cases of cT1aN0M0 NSCLC after surgical resections in the National Taiwan University Hospital from 2011 to 2015 were retrospectively reviewed. The predictive factors of interest were tumor size, tumor ground glass opacity (GGO) percentage on chest CT, and preoperative serum carcinoembryonic antigen (CEA) level. Logistic regression model was used to find predictive factors for nodal upstaging.
Results
A total of 770 patients were included in the study. Of these, 14 (1.8%) were found to have pN+ (nodal upstaging) after pulmonary resection. Larger tumor size, less tumor GGO percentage on chest CT, and higher preoperative serum CEA levels were significant predictors for nodal upstaging. On a pathological viewpoint, decreased lepidic component of the tumor, presence of visceral pleural invasion, and presence of lymphovascular invasion were also significantly correlated with nodal upstaging. With preoperative variables grouped into categorical data, tumor size ≥ 1.5 cm, CEA ≥ 3 ng/mL, and GGO < 25% had strong predictive values for lymph node metastases.
Conclusion
For NSCLC patients with clinical stage T1aN0M0, tumor size, preoperative serum CEA levels, and GGO percentage on CT scan were significant predictive factors for lymph node metastases after surgery. For patients with tumor size less than 1.5 cm, serum CEA levels less than 3 ng/mL, and GGO predominant tumors, avoiding lymph node dissection can be a reasonable approach. Sublobar resection, instead of standard lobectomy, may be a good alternative for this group of patients.

並列關鍵字

Non-small cell lung cancer ； nodal upstaging ； ground-glass opacity ； sublobar resection ； predictive factors

參考文獻

Aberle DR, Adams AM, Berg CD, et al. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med 2011;365:395–409.

Asamura H, Nakayama H, Kondo H, et al. Lymph node involvement, recurrence, and prognosis in resected small, peripheral, non–small cell lung carcinomas. Are these carcinomas candidates for video-assisted lobectomy? J Thorac Cardiovasc Surg 1996; 111:1125–34.

Bao F, Yuan P, Yuan X, Lv X, Wang Z, Hu J. Predictive risk factors for lymph node metastasis in patients with small size non-small cell lung cancer. J Thorac Dis. 2014; 6(12):1697-703

Callol L, Roig F, Cuevas A, et al. Low-dose CT: a useful and accessible tool for the early diagnosis of lung cancer in selected populations. Lung Cancer 2007; 56:217–21.

Chen K, Yang F, Jiang G, Li J, Wang J. Development and validation of a clinical prediction model for N2 lymph node metastasis in non-small cell lung cancer. Ann Thorac Surg. 2013; 96(5):1761-8