前哨淋巴結切片結合其他診斷工具於臨床上頸部轉移零期頭頸癌診斷正確率及結果之相關研究

Abstract

目的: 對於臨床上頸部轉移零期之頭頸癌病患，頸部淋巴理想的處置目前學界並沒有共識。過去大部份的耳鼻喉頭頸外科醫師多採取預防性頸淋巴結擴清手術處置，如此可能因而導致過度的治療。近年來有越來越多新的方法可以用來診斷臨床上頸部轉移零期之頭頸癌，包括電腦斷層(CT)、磁核共振(MRI)、超音波(US)、超音波導引細針穿刺(US-FNA)、正子攝影(PET)以及前哨淋巴結切片(SNB)檢查，本論文的目地在於詳細評估這些可以用於頸淋巴節轉移的工具。 方法: 本論文第一部份包括系統性的文獻回顧、統合分析，評估單一診斷工具的表現; 第二部份則透過假設性評估分析，比較結合多個診斷工具不同策略之陰性預測值; 第三部份聚焦於結合多個診斷工具之不同策略的經濟評估; 最後部份提出一份關於台灣結合前哨淋巴結切片檢查手術，於臨床上頸部轉移零期口腔癌病人的可行性報告。 結果: 在系統性的文獻回顧共收集了 73 篇文獻，CT 有10篇，MRI 有7篇，PET 有12篇，US 有 9篇，US-FNA 有 5篇，而SNB 則有 55篇。在統合分析顯示 US-FNA的敏感度為56% (95% 信賴區間 45%~67%)，SNB的敏感度為85% (82~87%)。CT, MRI, US 及 PET的敏感度分別為47% (38.2%~56.0%), 56.6% (39.8~71.9%), 63.3% (54.0~71.7%), 及48.3% (30.9~66.1%)，特異度分別為88.9% (82.0%~93.3%), 82.5% (39.8~71.9%), 79.1% (73.4~83.8%) 及86.2 % (76.9~92.1%)。CT, MRI, PET, US, US-FNA 及SNB 的 AUC 分別為0.81(0.56~1), 0.79(0.66~0.93), 0.83(0.69~0.96), 0.81(0.74~0.87), 0.97(0.85~1) 及0.98(0.96~0.99。假設性評估分析發現，採取 CT或 MRI加上SNB的策略，即使檢查前的頸淋巴轉移率高達60%，陰性預測值都可以高於85%。在決策分析方面，如不考慮成本，若檢查前的頸淋巴轉移率高於10%，CT或MRI 加上SNB的策略會有較高的效益值。若考量成本效益，CT-FNA 會有最低的成本花費，但是CT加上SNB仍有最佳的成本效益。在前哨淋巴結切片可行性研究，從2013年六月份至2014年三月份，共有11名口腔癌病患接受結合前哨淋巴結切片檢查的手術，所有的病人都可以發現前哨淋巴結（100%），所有的前哨淋巴結都位於頸部I~III 區域，四名病患前哨淋巴結術中發現有轉移，有一名病患追蹤一年頸部復發，因此前哨淋巴結切片檢查手術的敏感度估計為80%。 結論: 前哨淋巴結切片檢查是一項可靠的診斷工具; 結合前哨淋巴結切片檢查的手術於臨床上頸部轉移零期頭頸癌病人的處置未來可能有進一步發展的希望。

Background: The optimum management over the neck of clinical negative (cN0) head and neck cancer has been a debate for a long time. In the past, most head and neck surgeons did prophylactic neck dissection and potentially leaded to over-treatment. Since more and more modern diagnostic technologies are developing, the possibility of conservative treatment is increasing. The aim of this dissertation is to comprehensively assess multiple diagnostic tests, including traditional CT, MRI image, high resolution ultrasound (US), ultrasound guided fine needle aspiration(US-FNA), positron emission tomography (PET) and sentinel node biopsy (SNB). Materials and Methods: While the first part focuses on systematic review of individual diagnostic test, meta-analysis is also done to assess the diagnostic performance of each test. The second part uses hypothetical estimation of serial tests, which compares multiple diagnostic strategies, to evaluate the negative predictive value, over- and under treatment of each strategy. The third part uses decision modeling, which is under view point of patient and health care system, to assess the efficiency of the proposed diagnostic strategies. At the end, a feasibility study of sentinel node navigation surgery (SNNS) in Taiwan is presented. Results: In systematic review, total 73 studies were recruited. Ten studies fulfilled all inclusion criteria for CT, 7 studies for MRI, 12 studies for PET, 9 studies for US, 5 studies for US-FNA, 55 studies for SNB. In meta-analysis, the pooled estimates for sensitivity are 56% (95% confidence interval [CI], 45%~67%) and 85% (82~87%) for US-FNA and SNB respectively. The pooled estimates for sensitivity were 47% (95% confidence interval [CI], 38.2%~56.0%), 56.6% (39.8~71.9%), 63.3% (54.0~71.7%), 48.3% and (30.9~66.1%) for CT, MRI, US and PET respectively. The pooled estimates for specificity were 88.9% (82.0%~93.3%), 82.5% (39.8~71.9%), 79.1% (73.4~83.8%) and 86.2 % (76.9~92.1%) for CT, MRI, US and PET respectively. The AUC are 0.81(0.56~1), 0.79(0.66~0.93), 0.83(0.69~0.96), 0.81(0.74~0.87), 0.97(0.85~1) and 0.98(0.96~0.99) for CT, MRI, PET, US, US-FNA and SNB respectively. For hypothetical estimation, the NPV of CT/MRI then SNB strategies will still be higher than 85%, even the pre-test occult rate up to 60%. In decision analysis, without considering the cost, combined CT-SNB or MRI-SNB will have a higher expected utility if the pre-test occult metastasis rate is greater than10%. In cost-effectiveness analysis, the strategy of CT followed by US-FNA had the lowest price. The strategy of CT followed by SNB would be the most cost-effectiveness strategies. In feasibility study, between June 2013 and March 2014, eleven patients were recruited. At least one sentinel lymph node was identified in all patients (100%). All sentinel nodes were located at level I~ level III. The sensitivity of SNNS is 80% (4/5). Conclusions: SNB is reliable in evaluation of cN0 neck. SNNS could be a promising diagnostic and management strategy for cN0 HN cancer patients.