The Abscopal Effect Associated with Combined Pembrolizumab and Radiotherapy in Disseminated Locoregional/Metastatic Disease of Advanced Head and Neck Cancer- A Case Report

遠端效應發生於合併Pembrolizumab及放射線治療之侵犯性口腔癌病人－病例報告

郭家均(Chia-Chun Kuo) ； 高壽延(Shou-Yen Kao) ； 雷文天(Man-Tin Lui) ； 吳政憲(Cheng-Hsien Wu)

《臺灣口腔顎面外科學會雜誌》 28卷4期 (2017/12) Pp. 263-274

摘要

A 61 year-old male with the diagnosis of squamous cell carcinoma of right submandibular gland, and was found extensive neck recurrence and distant metastasis over skull base, peri-tracheal space, skin of neck, spine and lung soon after initial treatment Disseminated disease with ptosis, diplopia, orbital apex syndrome, bone pain over metastatic bony lesion, malignant hypercalcemia and conscious change were found, Palliative radiotherapy combined with immunotherapy (KEYTRUDA^®/Pembrolizumab) was planned to alleviate the clinical symptoms and signs, PET/CT scan demonstrated nearly complete remission of the disseminated lesions, not only the locoregional area, but also the distant metastatic foci at the end of combined immune-radiation therapy, The patient recovered well and with stable disease status in recent 1 year follow up, Abscopal effect was first proposed by Mole in 1953, which was defined as an action at a distance from the irradiated volume but within the same organism, The mechanism of abscopal effect remains a debate until the development of immunotherapy, The effect has been observed in patients undergoing systemic immunotherapy and palliative radiotherapy, and consists in a response of untreated lesions following a radiation cycle, The effect which is referred as an abscopal effect is immune-related, and the abscopal effect seems to occur through systemic immune activation stimulated by radiotherapy, and studies have suggested that radiation improves antitumoral response to immunotherapy through several mechanisms, including release of density of tumor-infiltrating lymphocytes, modulation of expression of immune checkpoint molecules, In our case, pembrolizumab as an immune checkpoint inhibitor was targeted on programmed cell death protein 1 (PD-1), which then activates the normal function of the T cell. Palliative radiotherapy was administered concurrently. The resolution of clinical symptoms and evidence from image studies concur the abscopal effect during the course of treatment. Tumor control in disseminated locally advanced head and neck cancer patients is generally poor, especially when it combined with distant metastasis. The abscopal effect exerted by concurrent immunotherapy and radiotherapy may be the ray of light in this difficult clinical scenario.

關鍵字

Immunotherapy ； Abscopal effect

並列摘要

61歲男性，診斷爲右側頷下腺鱗狀上皮細胞癌，在接受初步治療後發現廣泛性的頸部腫瘤復發，合併顱底、氣管周圍間隙，頸部皮膚及肺部等多處遠端轉移。瀰漫性的病灶造成腫瘤伴隨症候群，包含了上眼瞼下垂、複視、眶尖綜合症，骨轉移處疼痛、惡性高血鈣及意識改變。爲了緩解臨床症狀，我們使用了緩和性放射線治療合併免疫療法（KEYTRUDA^®/Pembrolizumab）。在經放射線治療合併免疫療法治療後，追縱的正子攝影顯示廣泛性病灶緩解，除了局部復發的區域以外，多處遠端轉移的病灶同樣也得到緩解。病人在一年的追蹤期間恢復良好，疾病目前也處於穩定狀態。Mole於1953年提出遠端效應，被定義爲同一生命體中，被放射線照射的物體以外所產生的效應。在當時，遠端效應的發生與機制存在爭議，直到近幾年免疫治療的發展，讓我們對遠端效應有較爲明確的認識。根據目前的病例報告，在合併使用放射線治療及免疫治療的身上，我們有較高的機會可以看到遠端效應的出現。遠端效應使得未經放射線治療的病灶區也可以得到緩解或改善。遠端效應目前被推估是免疫相關所引起的反應，並且這反應在合併使用免疫調節藥劑及放射線治療的情況下可能會被強化。經由多重免疫機制，包括腫瘤浸潤淋巴細胞的增加及免疫檢查哨分子的調節等，遠端效應可以得到較好的抗腫瘤效果。本病例中，免疫檢查哨抑制劑會作用在程序性細胞死亡蛋白，繼而使T細胞的正常功能可以被活化，同時，緩和性的放射線治療也同步給予。在治療過程中臨床症狀的緩解及治療過後的影像證據皆與遠端效應的產生相符。有鑒於在廣泛及侵犯性的口腔癌尤其合併遠端轉移的病人很難達到良好的腫瘤控制，且這類的病人預後相對較差，合併放射線治療及免疫治療後所產生的遠端效應可以爲這類的臨床困境開啓一盞明燈。

並列關鍵字

免疫療法 ； 遠端效應