氟-18去氧葡萄糖正子斷層造影預測以強度調控放射治療鼻咽癌患者之成果

2-[18F] Fluorodeoxyglucose Positron Emission Tomography in Predicting Outcome of Patients with Nasopharyngeal Carcinomas Treated by Intensity-Modulated Radiation Therapy

李永康(Jong-Kang Lee)

指導教授 ： 周明智

中山醫學大學/醫學院/醫學研究所/博士(2009年)

https://doi.org/10.6834/CSMU.2009.00002

摘要

鼻咽癌是一種上皮惡性腫瘤，與其他的頭頸部惡性腫瘤相比具有完全不同的流行病學、病原學、組織病理學、臨床特徵及治療方式。 它罕見於世界上大多數地區，但盛行於東南亞、地中海地區及中國南方地區。鼻咽癌在台灣的粗發生率約為每十萬人283人，其發生率排名於男性是第十名，女性是第十八名；死亡率的排名於男性是第九名，女性則是第十一名。雖然鼻咽癌的發生率比起其他癌症並不高，但是此病特別之處在於台灣等地區的盛行率大約是全世界平均發生率的25至50倍。鼻咽癌對放射線和化學治療藥物具有高度敏感性，放射治療長久以來就是鼻咽癌的主要治療方法，雖然依此治療方法對於早期患者可以獲得頗高的十年存活率，但是晚期患者接受放射治療之後仍然有顯著的局部復發及遠處轉移。找出能夠預測鼻咽癌接受放射及化學治療之後的預後的因素是很有臨床意義的，因為這將使得治療方式可以針對各個腫瘤的特性來量身訂做。傳統上預測治療結果的指標乃來自於臨床及病理表現，例如腫瘤和淋巴結期別、性別、年齡、有無侵犯腦神經、腫瘤的病理型態及放射治療的劑量和照野、原發腫瘤的體積、側咽擴散等等。即便經過仔細評估，但要可靠地將這些因素用之於預測各個患者的預後仍然有其困難之處。臨床，甚至病理的TNM分期和存活及復發形態之間的關聯性仍然不高，距離成為一個理想的預後指標還很遙遠。
由於對於偵測高葡萄糖代謝之腫瘤具有高靈敏度以及可以一次完成全身檢查，去氧葡萄糖正子斷層攝影已經普遍地應用於頭頸部惡性腫瘤的診斷及分期。近期的研究認為放射治療及或化學治療之前所作的去氧葡萄糖正子斷層攝影可以用來預測食道癌、子宮頸癌、肺癌以及鼻咽癌以外的頭頸部癌之治療反應或預後。然而，治療前的去氧葡萄糖正子斷層攝影是否能夠預測鼻咽癌患者接受放射治療及或化學治療的預後，卻鮮少有學者報告。本研究之目的在於探討利用正子斷層攝影最大標準攝取值 (maximum standardized uptake value) 測量鼻咽原發部位之非角化鱗狀上皮癌 (non-keratinizing squamous cell carcinoma) 之去氧葡萄糖攝取率與患者接受單獨強度調控放射治療 (IMRT, intensity- modulated radiotherapy) 或合併化學治療之後的局部控制 (local control) 及無病存活 (disease-free survival) 之間的關聯性。
本研究分析了112位罹患非角化鼻咽癌 (non-keratinizing nasopharyngeal carcinoma) 已在放射化學治療前接受去氧葡萄糖正子斷層攝影之患者資料。鼻咽癌原發部位之去氧葡萄糖攝取率是利用正子斷層攝影最大標準攝取值來量測。利用Kaplan-Meier method計算局部控制 (local control) 及無病存活 (disease-free survival)，並以 log-rank test評估。預後意義 (prognostic significance) 是利用單變量分析 (univariate analysis) 評估。分析的結果總計有21位患者接受
單獨強度調控放射治療，91位患者接受強度調控放射治療合併化學治療。有23位患者發生局部、區域、或遠處復發，其標準攝取值之平均值明顯高於其餘未發生復發患者之平均標準攝取值 (P < 0.001)。
單變量分析顯示原發腫瘤的T分期僅與局部控制有顯著相關性，而原發腫瘤之去氧葡萄糖最大標準攝取值則對於局部控制及無病存活二者都是顯著的預測值。T1-2組之3年局部控制率明顯高於T3-4組 (94% vs 76%, p=0.012)。以所有患者而言，最大標準攝取值小於或等於5之患者其3年局部控制及無病存活率都明顯高於最大標準攝取值大於5之患者。在T1-2患者當中，最大標準攝取值小於或等於5之患者其3年局部控制率明顯高於最大標準攝取值大於5之患者 (100% vs 87%, p=0.012) ，相似的結果亦發現於T3-4患者當中 (100% vs 59%, p=0.023)。
對於鼻咽癌患者而言，利用去氧葡萄糖正子斷層攝影測得之原發腫瘤標準攝取值是其接受單獨放射治療或同步放射化學療法後臨床預後之強有力的預後因子。去氧葡萄糖最大標準攝取值大於5是鼻咽癌患者臨床預後較差的標誌。本研究指出，對於鼻咽癌患者而言，其原發腫瘤的去氧葡萄糖標準攝取值或許是治療決策的一項重要指引。

關鍵字

去氧葡萄糖正子斷層造影 ； 鼻咽癌

並列摘要

Nasopharyngeal carcinoma (NPC) is an epithelial malignancy compared to other head and neck cancers by its epidemiology, histopathology, clinical characteristics, and treatment. It frequently happened in the Southeast Asia, the Mediterranean basin and the south China. The crude incidence of NPC in Taiwan is 283 cases per 100 thousands people each year. NPC is at the 10th position in incidence of cancer in men and eighteenth in women. As for the death rate, NPC is at the 9th position in men and eleventh in women. Though the incidence of NPC is not high compared to other cancers in Taiwan, the incidence is about 25 to 50 times higher than the general incidence of the world.
NPC is highly radiosensitive and chemosensitive. Radiotherapy has been the mainstay treatment for NPC and leads to a high 10-year survival rate if treated in the early-stage. However, there are significantly locoregional recurrence and distant metastases subsequent to radiotherapy in the advanced stage of disease. Identifying predictive factors of outcome in those patients after radio- and chemotherapies has great clinical implications because such factors may allow treatment to be specifically focused on the characteristics of individual tumors. Predictive factors of patient outcome in NPC have traditionally been derived from clinical and pathologic features, e.g., T and N stages, size and degree of fixation of neck nodes, sex, age, the presence of cranial nerve involvement, tumour’s histological type and the radiotherapy dosage and coverage, primary tumor volume, and parapharyngeal extension, etc. While detailed evaluation of these factors, difficulty remains to reliably predict the outcome of treatment in individual patients. The clinical, or even pathological TNM staging is still associated with a heterogeneous survival and relapse pattern, and is thus far from perfect as a prognostic indicator. Due to the high sensitivity in detecting tumors with high glucose metabolism and the capability of whole-body survey in a single examination, positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) has extensively been used in diagnosing the head and neck cancers. Previous studies have shown that use of 18F-FDG PET prior to use of radiotherapy and/or chemotherapy may be useful in predicting improvement in patients with esophageal cancer, cervical cancer, lung cancer, and in non-NPC head and neck cancer. However, the effectiveness of whole-body 18F-FDG PET examining NPC patients prior to use of radiotherapy has rarely been studied. Therefore, the purpose of this study was to investigate the association between the primary tumor FDG uptake, which was measured as the maximum standardized uptake value (SUVmax) at initial diagnosis, and local control (LC) and disease-free survival (DFS) in patients with nonkeratinizing NPC treated with intensity-modulated radiation therapy (IMRT) with or without chemotherapy.
One hundred and twelve patients with nonkeratinizing NPC who had received FDG-PET scan prior to radiation therapy combined with or without concurrent chemotherapy were recruited. Primary tumor FDG uptake was measured with the SUVmax. Actuarial LC and DFS and were calculated by the Kaplan-Meier method and evaluated with the log-rank test. The prognostic significance was assessed by univariate analysis.
There were 21 patients had definitive radiotherapy and 91 patients received radiotherapy combined with chemotherapy. The mean SUV was significantly higher in the 23 patients who presented with locoregional or distant failure than that in the remaining patients without any such failure (P < 0.001). By univariate analysis, T category showed significant correlations with 3-y LC while the SUVmax for the primary tumor was a significant predictor for both LC and DFS. The T1-2 group had a significantly higher 3-y LC than the T3-4 group (94% vs. 76%; P =.012). Patients with a low (≦ 5.0) SUV had a higher 3-y LC (P < 0.0001) and DFS (P < 0.0001) than those with a high (> 5.0) SUV. For T1-2 patients, 3-y LC was significantly higher in the low SUVmax group (100% vs. 87%; P = 0.012). A similar results were also found in T3-4 patients (100% vs. 59%; P= 0.023).
The SUV for the primary tumor was a powerful predictive factor of outcome in treating patients with NPC by CCRT or radiotherapy alone. A high 18F-FDG uptake (SUV > 5.0) was a marker for poor outcome in patients with NPC. Our study indicated that the SUVmax for primary tumors could be an important factor in choosing treatment for patients with NPC.

並列關鍵字

Positron Emission Tomography ； Nasopharyngeal Carcinoma

參考文獻

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