原文題目(出處)： 18FDG PET in squamous cell carcinoma of the oral cavity and oropharynx ： A study on inter- and intra observer agreement . J Oral Maxillofac Surg 2010;68:21-7.
原文作者姓名： Krabbe CA, Pruim J, Scholtens AM, Roodenburg JLN, Brouwers AH, Phan TTH, Agool A, Dijkstra PU
通訊作者學校： Department of Oral and Maxillofacial Surgery, University Medical Center Groningen
報告者姓名(組別)： 陳靜怡 CR2
報告日期： 99/02/19
內文：
Introduction
1. Oral SCC and oropharyngeal SCC 的 治 療 依 據 tumor size, infiltration of surrounding tissue and the absence or presence of metastaese 這幾點而有不同，
正確的對腫瘤分期對於適當的治療病人，將可能的treatment-related mobidity 降到最低非常重要。通常對Oral SCC and oropharyngeal SCC的分期依靠臨床 檢查、CT、MRI、Ultrasound with or without guided fine needle aspiration cytology
。
2. Fluorine-18 fluorodeoxyglucose (18FDG) positron emission tomography(PET) 已 被證實對診斷Oral SCC and oropharyngeal SCC是一項很有效的技術，特別是 在偵查locoregional and distant metastases。最近對將18FDG PET當作診斷Oral SCC and oropharyngeal SCC的primary imaging technique的支持越來越多。
優點：(1) sensitivity and specificity可與conventional imaging比擬甚至更好 (2) 可在同一次檢查中同時評估locoregional and distant metastases 缺點：(1) 缺乏解剖細節
(2) relative low resolution
以上缺點已藉由combined PET/CT imaging改善了。
3. 成為primary imaging technique除了sensitivity and specificity要好之外，同一觀 察者(intraobserver)不同時間的解讀與不同觀察者(interobserver)的解讀之間的 consistency也是必須的，這項品質條件與PET有否合併CT無關。要有效且一 致地判讀oral and oropharyngeal SCC 18FDG PET images是否需要一定程度的 專業能力，這個答案很重要，但令人意外的是對頭頸SCC 18FDG PET images inter- and intraobserver agreement大家的了解很少。技術發展的速度比評估 observer properties以及他們對影像判讀的影響要快，所以本研究的目的
(1) to evaluate the inter- and intraobserver agreement of the interpretations of
18FDG PET images
(2) to assess the influence of observer experience , tumor localization and tumor size on the agreement and sensitivity and specificity
Patients and Methods 1. Patients
數量：80, female: 31, male: 49, mean age: 61.3 Oral SCC: 62, Oropharyngeal SCC: 18
狀態：(1) newly diagnosed SCC of the oral cavity and /or oropharynx，在 1999~2004期間做過18FDG PET的檢查，在檢查前已經病理檢查確 診為SCC
(2) TNM staging
T: 由histological findings決定(全部)
N: 由histological findings決定(n=50, N+=23, 28 neck sides) 其次由cytological findings決定(n=10, N+=5, 5 neck sides)
以上皆無者由影像檢查(CT, MR, US etc)與clinical follow up(至 少1.5年)結果決定(n=20, N+=11, 18 neck sides)
N(+): 39 cases, 51 neck sides
M: ?, 頭 頸 以 外 的 malignancy: lung cancer(n=4), thyroid tumor(n=1), skeletal tumor(n=1), infraclavicular metastasis(n=1), esophagus carcinoma(n=1)
治療：(1) Primary Surgery (n=56) – Surgery only (n=28)
Surgery + supplementary RT (n=38) Neck dissection (n=50, 68 neck sides)
SND (39 neck sides)
Modified ND (28 neck sides) RND (1 neck sides)
(2) Primary RT (n=19) – RT only (n=12) RT+C/T (n=7) (3) No therapy (n=5) 2. 18FDG PET study
(1) 病人禁食至少4小時，IV注射FDG後90分鐘開使拍攝 (2) 使用相機
ECAT 951 – 31 planes/10.9-cm field, resolution: 6 mm full width at max.
ECAT HR+ -- 63 planes/15.5-cm field, resolution: 6 mm full width at max.
3. Study design (1) Observer – 4個
2 experienced nuclear medicine physicians (NMP)
– 15 years of experience (NMP I) and 5 years experience (NMP II) 2 residents in nuclear medicine
– 4 years of experience (R I) and 2 years experience (R II)
(2) 除了診斷為oral and oropharyngeal SCC 以外，進行檢查時其它資訊都沒有 提供
(3) 所有observer判讀影像時都是以任意(random order) 順序進行兩次，兩次之 間間隔3週，進行第二次判讀時第一次的結果並不會顯示出來，採用visual assessment，
(4) 評 估 primary tumor 與 有 無 cervical 及 distant metastases ， 對 abnormally increased 18FDG uptake 使用標準評分量表 (5-point scale) – definitely benign, probably benign, equivocal, probably malignant, 與 definitely malignant.
(5) 為 統 計 分 析 ， 將 definitely benign 與 probably benign 視 為 negative for malignancy而其餘視為positive for malignancy
4. Statistical analysis
(1) Inter- and intraobserver agreement
依primary tumor, cervical metastases per neck side 與distant malignancy三項判 讀結果分析這4位自身與彼此間判讀結果的一致性。以absolute agreement與 Cohen’s kappa來進行統計分析
Absolute agreement – the ratio of the finding in which agreement exists with the total findings
Cohen’s kappa – the ratio between chance-corrected observed agreement and chance-corrected perfect agreement
< 0.21 poor 0.21 ~0.4 fair 0.41~0.6 moderate 0.61~0.8 good
> 0.8 almost perfect agreement
以 第 一 次 判 讀 的 結 果 來 比 較 NPM I 與 NPM II, R I 與 R II interobserver agreement, 以 第一次和第二次判讀結果來比較四 位 observer的 intraobsever
agreement, 為 了解經驗是否會影響此agreement, 以 95% confidence interval analysis來分NMP與R的結果是否有顯著差異。
(2) Influence of tumor localization and tumor size
分析4位observer 對原發腫瘤位置、大小與頸部轉移的評估，藉此了解tumor localization 與tumor size對interobserver agreement的影響
(3) Sensitivity 與 specificity
以4位observer第一次判讀結果比對histological findings, 或cytological findings ( 若 沒 有 前 一 項 ) ， 或 follow-up 結 果 ( 若 前 兩 項 皆 無 ) 來 計 算 sensitivity 與 specificity, 並 比 較 NMP 與 R 的 結 果 以 了 解 經 驗 是 否 會 影 響 sensitivity 與 specificity
Sensitivity = true positive / (true positive + false negative) Specificity = true negative / (true negative + false positive) Results
1. Inter- and intraobserver agreement (table 2)
(1) The interosberver agreement between NMPs was greater than the interobserver
agreement between of Rs, 但只有cervical metastases達到顯著差異
(2) The intraobserver agreement of NMPs was greater than Rs, 但只有一個數值達 到顯著差異
(3) 兩個PET cameras之間沒有差異
2. Influence of tumor localization and tumor size (table 3 and table 4) (1) Tumor localization
當更精確的描述解剖位置被要求時，不論是primary tumor (oral cavity or oropharynx) 或cervical metastases (level I-V)，其interobserver agreement都下降 (只有level I cervical metastases absolute agreement 例外)。Level 5無kappa值因 為只有一個observer發現這個level的metastases。
(2) Tumor size
其中2個病例在檢查前其tumor就已經completely removed，其餘78個scan中，
有7個病例NMPs對其腫瘤的存在沒有共識，其中6個為stage T1，tumor 最大 直徑為20 mm，侵犯深度為5 mm，剩下1個為stage T2，最大直徑為31 mm，
侵犯深度為4 mm。Cervical metastases的size對interobserver agreement並沒有影 響，在10個不同意見的neck sides中只有一個neck side出現metastases，這個 lymph node 為25 mm。Sensitivity會隨tumor size增加而增加。
3. Sensitivity and specificity
(1) 經驗最少的R II 三項的sensitivity都比較其它三人低
(2) 因為正確地偵查到的malignancy少，false-positive results少，所以在cervical metastases與distant metastases/ second primary tumor 的specificity R II 比 其它人高
Discussion
1. Inter- and intraobserver agreement
本研究顯示18F-FDG PET在檢查oral 與oropharyngeal SCC有高 inter- and intraobserver agreement in SCC。
2. NMPs與Rs的經驗
NMPs的 inter- and intraobserver agreement 普遍比Rs高，雖然Rs的表現也在fair 到good之間，但經驗在intraobserver agreement 並沒有造成兩者間的差異，這 表示observer的經驗對判讀相同影像所發揮的影響是有限的。同樣在sensitivity and specificity, 經驗所扮演的角色也是有限的，在NMP之間並沒有差異，儘管 兩人之間有10年的資歷差別，而資深R的表現趨近於NMP，由於這個研究為 cross-sectional所有沒辦法呈現18F-FDG PET scans真實的學習曲線，資淺R的 sensitivity確實比其他三人低，所以本篇作者認為a short learning phase是存在的
，在此之後就達可接受的水準。其它的技術 (US-guided fine needle aspiration cytology, MRI, and CT)則被認為更加的依賴observer的經驗。對observer與經驗 依賴度較低可說是判讀18F-FDG PET影像一項優點。
3. Tumor localization
當對malignancy的位置要更精確的描述時, interobserver agreement就下降，只 有neck level I顯示有高interobserver agreement，這可能是因為這個區域在影像
上較易辨識的緣故，這種結果並不令人意外，因為18F-FDG PET影像缺乏解剖
細節。這項結果支持combining PET與CT(PET/CT)的附加價值，PET/CT比單 獨PET有更好的tumor localization又保有原PET的優點。
4. Tumor size
Tumor size 會 影 響 interobserver agreement 與 sensitivity of NMPs. The agreements increased with tumor size, with the exception of metastases smaller than 1 cm. These small cervical metastases showed high interobserver agreement despite the very low sensitivity. The high interobserver agreement resulted from the nondetection of the small metastases by both observers. Missing metastases 5 mm or smaller was not surprising against the background of the limited resolution of the PET camera.
5. Distant metastases or malignancy
18F-FDG PET for the initial staging of head and neck cancer is the possibility of evaluating the whole body for malignancy. All distant metastases/second primary tumors were detected by both NMPs, except for one small superficial esophagus carcinoma. Disagreement, mostly for suspected malignancy in the lung or mediastinum, was present in 12 scans, all without proven second primary tumors or distant metastases, highlighting the known false-positive risk of 18F-FDG PET.
6. Limitation of this study
(1) Most notably for our study, the drawback was the influence of the distribution of malignancy. The kappa values tend toward lower values when the distribution is asymmetric. In the present study, the presence of malignancy in the head and body was very asymmetrically distributed: 98% and 10%, respectively. Thus, despite the high absolute agreement for detecting primary tumor and distant metastases, comparable to the agreement for detecting
cervical metastases, the kappa values of the primary tumor and distant metastases were lower than those for cervical metastases.
(2) The histologic findings of the surgical specimens were used to determine the tumor size. However, for some patients with malignancy, surgical specimens were not obtained. For these patients, the tumor size was determined by CT, MRI, or US performed at diagnosis of the malignancy. The measured diameter was used as the malignancy size. Thus, it is possible that the measurements for these malignancies were somewhat overestimated.
7. PET/CT與PET alone
It could be argued that an analysis of PET data is superfluous in the PET/CT era.
However, PET/CT is a combination of 2 imaging techniques, each with its own characteristics. To understand the added value of the combination, the value of each of the components should be known. The results of our study have revealed that the interpretation of PET data is relatively observer experience independent;
however, 18F-FDG PET is lacking for locating a tumor. As such, the present study provides a strong argument for the use of PET/CT in the evaluation of SCC of the head and neck.
Conclusion
(1) 18FDG PET images of SCC of the oral cavity or oropharynx在偵測malignancy方 面表現出良好的inter-與intraobserver agreement
(2) Observer的經驗對observer agreement的影響有限
(3) 即使是在困難的頭頸區域，所得到的影像仍可被可靠地的判讀
(4) 若要更精確描述tumor anatomic localization，則observer agreement會下降 (5) Observer agreement 與sensitivity隨tumor size 增加而增加，與經驗無關，這表
示在偵測small cervical metastases 18FDG PET得能力有限。
題號 題目
1 下列何種檢查非利用放射線?
(A) Whole body Bone scan (B) PET
(C) MR
(D) Scintigraphy 答案( C) 出處：
題號 題目
2 Oral SCC TNM 分期下列何者正確?
(A) Tumor size > 6 cm為T4
(B) 同側多個lymph node轉移, 小於6 cm為N2b (C) 對側lymph node 轉移為N2a
(D) Carcinoma in situ 為T0 答案( B) 出處：
