蘇端玉 侯如蓉廈門大學(xué)附屬中山醫(yī)院腫瘤放療科,福建廈門361004
口服營(yíng)養(yǎng)支持在鼻咽癌放療患者中的臨床研究
蘇端玉 侯如蓉
廈門大學(xué)附屬中山醫(yī)院腫瘤放療科,福建廈門361004
目的探討口服營(yíng)養(yǎng)支持對(duì)鼻咽癌放療患者營(yíng)養(yǎng)狀況及副反應(yīng)的影響。方法鼻咽癌初治患者83例,放療前NRs 2002評(píng)分<3分,隨機(jī)分為營(yíng)養(yǎng)支持組40例和無營(yíng)養(yǎng)支持組43例,放療后1周內(nèi)再次行NRs 2002評(píng)分,比較兩組的營(yíng)養(yǎng)指標(biāo)和放療副反應(yīng)情況。結(jié)果83例鼻咽癌患者根治性放療后NRs 2002評(píng)分≥3分者53例,營(yíng)養(yǎng)風(fēng)險(xiǎn)發(fā)生率為63.9%,營(yíng)養(yǎng)支持組營(yíng)養(yǎng)不良發(fā)生率更低(52.5%vs 74.4%,P<0.05)。兩組血紅蛋白(Hb)、白蛋白(ALB)、淋巴細(xì)胞數(shù)(LYM)放療后均有顯著下降,但營(yíng)養(yǎng)支持組放療后的Hb、體重指數(shù)(BMI)較無營(yíng)養(yǎng)支持組高,體重下降比例更低,差異均有統(tǒng)計(jì)學(xué)意義(P<0.05)。無營(yíng)養(yǎng)支持組的2/3級(jí)口腔黏膜炎、咽食管炎發(fā)生率較營(yíng)養(yǎng)支持組高,放療療程更長(zhǎng)(P<0.05)。結(jié)論鼻咽癌放療患者營(yíng)養(yǎng)風(fēng)險(xiǎn)發(fā)生率較高,口服營(yíng)養(yǎng)支持可以減少體重丟失,減輕急性放射性口咽黏膜反應(yīng),進(jìn)而提高患者的生活質(zhì)量和腫瘤控制率。因此口服營(yíng)養(yǎng)支持是一種值得臨床推廣的方便、經(jīng)濟(jì)、有效的腸內(nèi)營(yíng)養(yǎng)方法。
鼻咽腫瘤;放射治療;營(yíng)養(yǎng)風(fēng)險(xiǎn);口服營(yíng)養(yǎng)補(bǔ)充;不良反應(yīng)
營(yíng)養(yǎng)不良和腫瘤消耗是癌癥患者存在的普遍現(xiàn)象,其發(fā)生率達(dá)30%~80%[1]。頭頸部腫瘤患者因吞咽困難、吞咽疼痛和抑郁情緒而導(dǎo)致營(yíng)養(yǎng)狀況更遭[2]。營(yíng)養(yǎng)不良可以直接導(dǎo)致腫瘤患者住院時(shí)間延長(zhǎng)、抗腫瘤治療敏感性減弱、并發(fā)癥增加、治療費(fèi)用提高、生活質(zhì)量以及生存率下降[3]。因此必須重視頭頸部腫瘤患者的營(yíng)養(yǎng)狀態(tài)和治療。鼻咽癌是我國(guó)南方地區(qū)的高發(fā)腫瘤之一,放療是鼻咽癌的重要治療手段,放療引起的口咽、食管黏膜反應(yīng)、口干、味覺改變等副反應(yīng)降低了患者的食欲和免疫功能,從而影響放療的進(jìn)行和治療效果,降低患者的生存質(zhì)量。本研究探討了口服營(yíng)養(yǎng)支持對(duì)鼻咽癌放療患者營(yíng)養(yǎng)狀況及放療副反應(yīng)的影響,以期為臨床制訂營(yíng)養(yǎng)支持治療方案提供依據(jù)?,F(xiàn)報(bào)道如下。
1.1 一般資料
選擇2013年1月1日~2015年10月31日就診于我院的初治鼻咽癌患者83例,男58例,女25例,年齡23~70歲,中位年齡49歲?;颊呔?jīng)組織學(xué)和免疫組化檢查確診為鼻咽未分化非角化性癌,按照AJCC鼻咽癌分期標(biāo)準(zhǔn)(第7版,2010),Ⅰ期3例,Ⅱ期13例,Ⅲ期33例,Ⅳ期34例。放療前營(yíng)養(yǎng)風(fēng)險(xiǎn)篩查量表2002(nutritional risk screening 2002,NRs 2002)評(píng)分均<3分。83例患者隨機(jī)分為營(yíng)養(yǎng)支持組(40例)和無營(yíng)養(yǎng)支持組(43例),所有患者均簽署知情同意書,兩組均接受根治性調(diào)強(qiáng)放療,鼻咽靶區(qū)劑量為66~75 Gy,平均劑量70 Gy,放療療程(第1次放療到放療結(jié)束的天數(shù))的中位時(shí)間為47 d,其中50例患者接受過新輔助化療2~3周期,方案為“紫杉醇、順鉑/奈達(dá)伯”或“吉西他濱、順鉑/奈達(dá)伯”。57例接受單藥鉑類的同期化療。9例接受“尼妥珠單抗”靶向治療。放療結(jié)束1周內(nèi)再次NRs2002評(píng)定。兩組患者的臨床資料(性別、年齡、分期、放療劑量、有無化療、靶向治療)比較,差異均無統(tǒng)計(jì)學(xué)意義(P>0.05),具有可比性。見表1。
1.2 營(yíng)養(yǎng)支持方法
根據(jù)腫瘤患者營(yíng)養(yǎng)指南,設(shè)定營(yíng)養(yǎng)支持組目標(biāo)能量30~35 kcal/(kg·d),蛋白質(zhì)1.5~2.0 g/(kg·d),碳水化合物3.0~4.0 g/(kg·d)),脂肪1.0~1.5 g/(kg·d),液體量30~40 mL/(kg·d)),每天統(tǒng)計(jì)日常飲食產(chǎn)生的熱量和各種營(yíng)養(yǎng)素含量,然后予安素(雅培制藥生產(chǎn),400 g/罐,注冊(cè)證號(hào)H20130320)補(bǔ)充不足的能量和營(yíng)養(yǎng)素。無營(yíng)養(yǎng)支持組則除日常飲食外無額外補(bǔ)充營(yíng)養(yǎng)素。
1.3 評(píng)價(jià)指標(biāo)
1.3.1 營(yíng)養(yǎng)指標(biāo)觀察兩組放療后的營(yíng)養(yǎng)風(fēng)險(xiǎn)發(fā)生率(放療結(jié)束后1周內(nèi)NRs 2002測(cè)評(píng),具體判定詳見1.3.3)和體重下降比例(放療開始前和結(jié)束后1周內(nèi)的體重變化/放療前1周內(nèi)的體重),以及兩組放療前后(1周內(nèi))血紅蛋白(Hb)、白蛋白(ALB)、淋巴細(xì)胞計(jì)數(shù)(LYM)、體重指數(shù)(BMI)的變化情況。
1.3.2 放療副反應(yīng)按照RTOG急性放射損傷分級(jí)標(biāo)準(zhǔn)[4],觀察兩組的急性皮炎、口腔黏膜反應(yīng)、咽食管黏膜反應(yīng)、涎腺反應(yīng)(口干)和血細(xì)胞下降情況。
1.3.3 營(yíng)養(yǎng)風(fēng)險(xiǎn)評(píng)定營(yíng)養(yǎng)風(fēng)險(xiǎn)評(píng)定采用歐洲腸外腸內(nèi)營(yíng)養(yǎng)學(xué)會(huì)(ESPEN)2002年制訂的NRs 2002[5],主要包含營(yíng)養(yǎng)狀況受損評(píng)分(0~3分);疾病嚴(yán)重程度評(píng)分(0~3分);年齡評(píng)分,即在前兩項(xiàng)評(píng)分基礎(chǔ)上若年齡≥70歲者加1分;總分為0~7分。當(dāng)NRs 2002評(píng)分≥3分時(shí)判斷為有營(yíng)養(yǎng)風(fēng)險(xiǎn)。
1.4 統(tǒng)計(jì)學(xué)方法
采用SPSS 19.0統(tǒng)計(jì)學(xué)軟件對(duì)數(shù)據(jù)進(jìn)行分析。計(jì)量資料以均數(shù)±標(biāo)準(zhǔn)差(x±s)表示,采用t檢驗(yàn),計(jì)數(shù)資料采用χ2檢驗(yàn),P<0.05為差異有統(tǒng)計(jì)學(xué)意義。
表1 兩組臨床資料比較[n(%)]
83例鼻咽癌患者根治性放療后NRs 2002評(píng)分≥3分者53例,營(yíng)養(yǎng)風(fēng)險(xiǎn)發(fā)生率為63.9%,其中營(yíng)養(yǎng)支持組21例(52.5%),無營(yíng)養(yǎng)支持組32例(74.4%)。
表2 組內(nèi)放療前后營(yíng)養(yǎng)指標(biāo)比較(x±s)
表3 組間放療前后營(yíng)養(yǎng)指標(biāo)比較(±s)
表3 組間放療前后營(yíng)養(yǎng)指標(biāo)比較(±s)
時(shí)間Hb(g/L)ALB(g/L)LYM(×109/L)BMI(kg/m2)體重下降(%)營(yíng)養(yǎng)風(fēng)險(xiǎn)發(fā)生率[n(%)]無營(yíng)養(yǎng)支持組營(yíng)養(yǎng)支持組組別n放療前43 40 t值P值放療后無營(yíng)養(yǎng)支持組營(yíng)養(yǎng)支持組43 40 χ2/t值P值135.3±12.2 136.9±13.2 -0.433 0.665 122.9±11.4 130.4±10.9 -6.130 0.002 43.4±3.1 44.2±3.3 -1.070 0.289 40.9±3.7 41.8±3.4 -1.154 0.252 1.9±0.6 1.9±0.6 0.000 1.000 0.7±0.3 1.1±0.3 -5.640 0.000 23.4±3.3 24.3±2.9 -0.399 0.691 21.1±5.4 23.5±2.3 -3.423 0.001 6.5±2.4 2.1±2.0 4.230 0.001 32(74.4)21(52.5)4.310 0.043
2.1 營(yíng)養(yǎng)指標(biāo)變化
兩組Hb、ALB、LYM放療后均有下降(P<0.05);營(yíng)養(yǎng)支持組放療后Hb、BMI較無營(yíng)養(yǎng)支持組高,差異有統(tǒng)計(jì)學(xué)意義(P<0.05);營(yíng)養(yǎng)支持組放療后體重下降比例較無營(yíng)養(yǎng)支持組低,差異有統(tǒng)計(jì)學(xué)意義(P<0.05)。見表2、3。
2.2 放療副反應(yīng)
急性放療副反應(yīng)主要為1~3級(jí)急性放射性皮炎[分別為79.5%(66/83)、13.3%(11/83)、7.2%(6/83)]、口腔黏膜炎[分別為36.1%(30/83)、46.3%(38/83)、17.6%(15/83)]和咽食管炎[分別為39.8%(33/83)、46.1%(38/83)、14.1%(12.83)],1~2級(jí)涎腺損傷[分別為62.7%(52/83)、37.3%(31/83)]和1~4級(jí)白細(xì)胞降低[分別為16.8%(14/83)、18.1%(15/83)、0%(0/83)、1.2%(1/83)],血紅蛋白和血小板降低不明顯。兩組比較結(jié)果顯示,無營(yíng)養(yǎng)支持組的2/3級(jí)口腔黏膜炎、咽食管炎發(fā)生率較營(yíng)養(yǎng)支持組高,差異有統(tǒng)計(jì)學(xué)意義(P<0.05,表4)。無營(yíng)養(yǎng)支持組因治療中斷發(fā)生率更高導(dǎo)致療程較營(yíng)養(yǎng)支持組長(zhǎng)(χ2=6.018,P<0.05,表1)。
表4 兩組放療副反應(yīng)比較[n(%)]
營(yíng)養(yǎng)支持已成為腫瘤治療的重要組成部分,理想的營(yíng)養(yǎng)支持應(yīng)當(dāng)基于對(duì)患者營(yíng)養(yǎng)狀況的準(zhǔn)確評(píng)估。目前營(yíng)養(yǎng)篩查的方法很多,本研究采取2002年歐洲營(yíng)養(yǎng)學(xué)會(huì)提出的營(yíng)養(yǎng)風(fēng)險(xiǎn)篩查方案(nutritional risk screening 2002,NRs 2002),該方案主要用于住院患者的營(yíng)養(yǎng)風(fēng)險(xiǎn)篩查,其突出的優(yōu)點(diǎn)在于能預(yù)測(cè)營(yíng)養(yǎng)風(fēng)險(xiǎn),并能前瞻性地動(dòng)態(tài)判斷患者營(yíng)養(yǎng)狀態(tài)變化,便于及時(shí)反饋患者的營(yíng)養(yǎng)狀況,并為調(diào)整營(yíng)養(yǎng)支持方案提供證據(jù)[6]??诜I(yíng)養(yǎng)補(bǔ)充(ONS)為特殊醫(yī)療目的經(jīng)口攝入一般食品以外的口服營(yíng)養(yǎng)補(bǔ)充劑,以達(dá)到增加能量和營(yíng)養(yǎng)素的攝入量,經(jīng)濟(jì)、方便,患者易于接受。
頭頸部腫瘤在初診時(shí)約有3%~52%存在營(yíng)養(yǎng)不良[7],這主要是由腫瘤本身引起。而手術(shù)、放療、化療或以上措施的綜合治療進(jìn)一步影響了患者的營(yíng)養(yǎng)攝入。文獻(xiàn)報(bào)道,頭頸部腫瘤患者在單純放療或同期放化療期間約有44%~88%出現(xiàn)營(yíng)養(yǎng)不良[8,9]。本組鼻咽癌患者根治性放療后NRs 2002評(píng)分≥3分者53例,營(yíng)養(yǎng)風(fēng)險(xiǎn)發(fā)生率為63.9%,提示鼻咽癌放療患者存在較高的營(yíng)養(yǎng)風(fēng)險(xiǎn)發(fā)生率,故應(yīng)重視并及時(shí)評(píng)估患者的營(yíng)養(yǎng)狀況。
在頭頸部腫瘤研究中通常將營(yíng)養(yǎng)不良定義為最近1~6月體重下降大于5%~10%,或是BMI小于18.5~20 kg/m2[10,11]。本研究發(fā)現(xiàn)無營(yíng)養(yǎng)支持組的營(yíng)養(yǎng)風(fēng)險(xiǎn)發(fā)生率顯著高于營(yíng)養(yǎng)支持組(74.4%vs 52.5%,P<0.05),且放療后體重下降比例更高,BMI更低。體重下降影響患者的治療耐受性、降低生存質(zhì)量和縮短生存時(shí)間[1,11,12]。Du等[13]研究發(fā)現(xiàn),嚴(yán)重體重下降(治療期間體重下降≥10%)是總生存和無遠(yuǎn)處轉(zhuǎn)移生存不良的獨(dú)立預(yù)后因素。Ouyang等[14]對(duì)1778例鼻咽癌接受放(化)療患者治療前的體重指數(shù)進(jìn)行傾向匹配分析顯示,BMI<18.5 kg/m2組的疾病相關(guān)生存、總生存、無遠(yuǎn)處轉(zhuǎn)移生存方面劣于正常BMI(18.5~22.9 kg/m2),而超重(22.9~27.5 kg/m2)和肥胖組(≥27.5 kg/m2)與正常組相似。因此重視營(yíng)養(yǎng)攝入,減少治療后體重丟失,有益于腫瘤患者的治療和預(yù)后。
血紅蛋白、白蛋白和淋巴細(xì)胞計(jì)數(shù)等血液指標(biāo)也常被用于評(píng)估營(yíng)養(yǎng)狀況。已有研究發(fā)現(xiàn)低蛋白血癥是進(jìn)展期頭頸部腫瘤同期放化療的獨(dú)立預(yù)后因素[15]。但近幾年有學(xué)者研究發(fā)現(xiàn)在頭頸部腫瘤前白蛋白是較白蛋白更為敏感的指標(biāo)[16,17]。淋巴計(jì)數(shù)低于(1.2~1.3)× 109/L被認(rèn)為是營(yíng)養(yǎng)不良的另一個(gè)指標(biāo)[18]。Mc Closkey等[19]發(fā)現(xiàn),血紅蛋白低于12 g/dL和總放療時(shí)間均是頭頸部腫瘤同期放化療后局部復(fù)發(fā)的預(yù)后指標(biāo)。但Mary等[20]對(duì)該組病例的進(jìn)一步隨訪和重新分析,結(jié)果單因素分析顯示,血紅蛋白仍存在統(tǒng)計(jì)學(xué)差異,但多因素分析結(jié)果只有總放療時(shí)間和治療前的理想體重比是局部復(fù)發(fā)的預(yù)后因素。兩次分析血紅蛋白的分界點(diǎn)不同可能是造成此差異的原因。本研究發(fā)現(xiàn)兩組放療后血紅蛋白、白蛋白、淋巴細(xì)胞計(jì)數(shù)均下降,但營(yíng)養(yǎng)支持組放療后的血紅蛋白和淋巴細(xì)胞計(jì)數(shù)較無營(yíng)養(yǎng)支持組高,差異有統(tǒng)計(jì)學(xué)意義。
有文獻(xiàn)報(bào)道[21,22]鼻咽癌調(diào)強(qiáng)放療2級(jí)以上的急性黏膜炎發(fā)生率約63%~83%。本研究2/3級(jí)急性放射性口腔黏膜炎和咽食管炎的發(fā)生率分別為63.9%(53/83)、60.2%(50/83),與文獻(xiàn)報(bào)道相似,而營(yíng)養(yǎng)支持組的2/3級(jí)急性放射性口腔黏膜炎和咽食管炎的發(fā)生率較無營(yíng)養(yǎng)支持組顯著降低。2級(jí)以上的急性黏膜反應(yīng)和口干影響患者的營(yíng)養(yǎng)攝入,從而降低患者的免疫功能、體重,甚至導(dǎo)致治療中斷、延長(zhǎng)放療療程。本研究也顯示無營(yíng)養(yǎng)支持組的放療療程較營(yíng)養(yǎng)支持組延長(zhǎng),差異有統(tǒng)計(jì)學(xué)意義(P<0.05)。已有文獻(xiàn)報(bào)道頭頸部鱗癌放療療程是局部治療失敗的主要預(yù)后指標(biāo)[19,20]。因此,早期、及時(shí)營(yíng)養(yǎng)干預(yù),減輕急性放射損傷,可能提高腫瘤的局控率。
預(yù)防性的鼻飼管置入術(shù)或經(jīng)皮胃造瘺術(shù)是目前常用的頭頸部腫瘤腸內(nèi)營(yíng)養(yǎng)方法。有文獻(xiàn)報(bào)道[23]頭頸部腫瘤放(化)療時(shí)預(yù)防性鼻飼管置入患者在治療結(jié)束6周時(shí)的體重下降和三角肌厚度較預(yù)防性胃造瘺術(shù)患者差,但兩種腸內(nèi)營(yíng)養(yǎng)方法帶來的并發(fā)癥和患者的滿意度無差異,而胃造瘺術(shù)的費(fèi)用是鼻飼管置入術(shù)的10倍以上,且胃造瘺管依賴的時(shí)間更長(zhǎng)。另外預(yù)防性胃造瘺術(shù)因無需吞咽,吞咽肌群鮮少活動(dòng),研究發(fā)現(xiàn)胃造瘺術(shù)后吞咽困難發(fā)生率較鼻飼管置入高[24]。因此胃造瘺術(shù)和鼻飼管置入孰優(yōu)孰劣,目前尚無確定標(biāo)準(zhǔn)。Hutcheson KA等[25]的研究發(fā)現(xiàn)咽部腫瘤放(化)療期間堅(jiān)持經(jīng)口攝入或堅(jiān)持吞咽功能鍛煉,放(化)療后可以獲得更好的長(zhǎng)期飲食,依賴胃造瘺管的時(shí)間更短。因此口服營(yíng)養(yǎng)支持不失為一種有效、簡(jiǎn)便、經(jīng)濟(jì)的腸內(nèi)營(yíng)養(yǎng)方法,值得臨床推廣,并予個(gè)體化的飲食指導(dǎo)也有助于提高患者的營(yíng)養(yǎng)攝入、營(yíng)養(yǎng)狀態(tài)和生活質(zhì)量。
綜上所述,鼻咽癌放療患者營(yíng)養(yǎng)風(fēng)險(xiǎn)發(fā)生率較高,口服營(yíng)養(yǎng)支持可以減少體重丟失,減輕急性放射性口咽黏膜反應(yīng),進(jìn)而提高患者的生活質(zhì)量和腫瘤控制率。因此口服營(yíng)養(yǎng)支持是一種值得臨床推廣的方便、經(jīng)濟(jì)、有效的腸內(nèi)營(yíng)養(yǎng)方法。
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Clinical study of oral nutrition in nasopharyngeal carcinoma patients treated with radiotherapy
SU DuanyuHOU Rurong
Department of Radiotherapy,Zhongshan Hospital Affiliated to Xiamen University,Xiamen361004,China
Objective To investigate the effects of oral nutritional supplementation on nutritional status and side effects of nasopharyngeal carcinoma patients after radiotherapy.Methods A total of 83 nasopharyngeal carcinoma patients(Nutrition risk scores<3)were assigned to oral nutrition support group(ONS-group,n=40)and non-oral nutrition support group(N-ONS-group,n=43).Nutrition risk of these patients was assessed again by Nutritional Risk Screening 2002(NRs2002)wthin 1 week after radiotherapy.Clinical data,nutritional index and adverse reaction were compared between two groups.Results Nutritional risk was found in 53 casess of all patients(63.9%),while the incidence of malnutrition was lower in ONS-group(52.5%vs 74.4%,P<0.05).Hemoglobin level(Hb),albumin level(ALB)and lymphocyte count(LYM)were significantly decreased after radiotherapy in both groups,but Hb and body mass index(BMI)after radiotherapy in ONS-group were higher than that of N-ONS-group,and weight loss ratio was lower(P<0.05).N-ONS-group occurred more grade 2/3 radiation oropharyngeal mucosal toxicity,swallow esophagitis(P<0.05),and was longer in the course of radiotherapy because of the interruption of treatment(P<0.05).Conclusion The incidence of nutrition risk is higher in patients with nasopharyngeal carcinoima after radiotherapy.Oral nutrition supplymentation can reduce weight loss and the acute irradiation oropharyngeal mucosa toxicity,which may improve the quality of life of patients and tumor control rate.So oral nutritional supplymentation is a convenient,economical and effective method of enteral nutrition.
Nasopharyngeal carcinoma;Radiotherapy;Nutritional risk;Oral nutritional supplymentation;Adverse reaction
R739.63;R473.73
B
1673-9701(2016)26-0073-05
2016-06-24)