局部晚期頭頸癌病人同步化放療期間補充富含植化素蔬果汁減緩口腔黏膜炎之效用

Abstract

頭頸癌 (head and neck cancer, HNC) 是全球第六大常見癌症，也是國人癌症發生率及死亡率排名皆為第六位的癌症。同步化放療 (concurrent chemo-radiotherapy, CCRT) 則是局部晚期頭頸癌 (locally advanced head and neck cancer) 的主要治療方法，然而，CCRT常導致嚴重的營養相關副作用，對病人的營養素及液體攝取影響甚鉅。尤其口腔黏膜炎（oral mucositis, OM）是最痛苦的併發症，會導致疼痛、吞嚥困難、體重減輕，嚴重甚至會造成療程中斷，影響療效。CCRT造成口腔黏膜炎的主要機轉，可能是由於放射線損傷及化療藥物毒性，促使上皮細胞產生活性氧物質 (reactive oxygen species, ROS)，增加氧化壓力，活化核轉錄因子 （nuclear factor kappa-B, NF-κB），造成促發炎細胞激素的分泌增加，導致上皮黏膜細胞的損傷。蔬菜和水果含有大量的植物化學物質 (簡稱植化素) (phytochemical)，如多酚 (polyphenol) 和類胡蘿蔔素 (carotenoid)，它們具有抗氧化和抗發炎的特性，並可刺激細胞 DNA 的修復。然而，關於蔬菜和水果減緩口腔黏膜炎的效益，目前研究仍極為缺乏。因此，本研究以富含植化素蔬果汁 (vegetable and fruit juice, VFJ) 的介入方式，評估局部晚期頭頸癌病人CCRT期間補充蔬果汁是否具有減緩口腔黏膜炎的效用。本研究收案 49 名接受 CCRT 的局部晚期頭頸癌病人，所有受試者治療前皆由營養師提供營養諮詢，後續每週進行電話追蹤。蔬果汁使用12種蔬菜、水果攪打製作，每100 mL 總多酚含量為64.6 mg沒食子酸當量，類胡蘿蔔素主要為β-胡蘿蔔素和茄紅素。蔬果汁介入組 (VFJ 組)（25 位受試者）在 CCRT 前兩週和6-7 週的治療期間，每天提供 600 mL 蔬果汁，5天/週；而對照組 （24 位受試者）除了未提供蔬果汁外，其他專業團隊常規照護則與VFJ組相同。比較兩組受試者血液生化檢測、體位測量、飲食攝取量及營養影響症狀 (nutrition impact symptom, NIS) 等數據的差異；以世界衛生組織口腔黏膜炎評估表（The World Health Organization Oral Toxicity Scale）進行口腔黏膜炎嚴重等級的評估。研究結果顯示，VFJ 組平均每天蔬果汁飲用量為 357~589 mL；基線及CCRT第6週，兩組在生化數據、營養素攝取量和體重減輕上沒有顯著差異。CCRT的第3週及第6週，VFJ 組的口腔黏膜炎嚴重級數分佈及平均分數皆顯著較對照組為低。CCRT第6週，VFJ 組 (64.0%) 潰瘍性口腔黏膜炎 (WHO grade ≥ 2) 的發生率明顯低於對照組 (95.8%)。多變量邏輯斯迴歸分析 (Multiple logistic regression analysis) 顯示，蔬果汁的飲用明顯可降低潰瘍性口腔黏膜炎發生的風險。此外，蔬果汁減輕了口腔疼痛及口乾的症狀強度，佐證蔬果汁在減緩口腔黏膜炎的效用。綜上所述，飲用富含植化素（包括多酚和類胡蘿蔔素）的新鮮攪打蔬果汁，可有效減緩局部晚期頭頸癌病人 CCRT造成口腔黏膜炎的嚴重程度。

Head and neck cancer (HNC) is considered the sixth most common cancer worldwide. In Taiwan, HNC is the sixth prevalent cancer and ranked the sixth cause of cancer death. Concurrent chemoradiotherapy (CCRT) is the standard therapeutic approach for patients with locally advanced HNC. However, the treatment can cause severe side effects with relevant impacts on nutrition and hydration. Oral mucositis (OM) is the most painful complication, leading to dysphagia, body weight loss, and even interruption of the course of treatment. CCRT-induced OM may be due to the generation of reactive oxygen species (ROS) that increase oxidative stress and subsequently induce the release of inflammatory cytokines. Vegetables and fruits contain large amounts of phytochemicals, such as polyphenols and carotenoids, which contribute to antioxidant and anti-inflammatory properties in plant foods and stimulate DNA repair. However, the beneficial effects of vegetables and fruits on OM alleviation are still rare in the literature. Hence, this study aimed to evaluate the effectiveness of phytochemical-rich vegetable and fruit juice (VFJ) consumption in preventing CCRT-induced OM among patients with locally advanced HNC. Forty-nine patients with locally advanced HNC undergoing CCRT were enrolled. All patients received nutritional consultation before CCRT and weekly follow-up. Total polyphenols content was 64.6 mg gallic acid equivalents per 100mL of the VFJ, and the main carotenoids were β-carotene and lycopene. The VFJ group (25 patients) received 600 mL/day of VFJ 5 days/week for two weeks preceding CCRT and during CCRT, and the control group (24 patients) did not. Changes in anthropometric, dietary, and laboratory profiles were compared. The assessment of OM was based on the World Health Organization (WHO) scoring system. The results showed that the mean daily consumption of the VFJ was 357 to 589 mL for the VFJ group. Changes in body weight, albumin, and energy intake were not significantly different between the two groups. The incidence of ulcerative OM was significantly lower in VFJ (64.0%) than in control (95.8%) subjects at week 6 of CCRT. Multiple logistic regressions revealed that VFJ consumption correlated significantly with lower risks of ulcerative OM. This was further confirmed by the observation that VFJ had reduced the intensity of oral pain and dry mouth symptoms. In conclusion, consumption of VFJ rich in phytochemicals, including total polyphenols and carotenoids, effectively alleviates the severity of CCRT-induced OM among patients with locally advanced HNC.