胡洪林,羅 興,曾 銘
(四川省醫(yī)學(xué)科學(xué)院·四川省人民醫(yī)院腫瘤中心,四川 成都 610072)
低劑量放療在老年局部晚期喉及下咽鱗癌中的療效研究
胡洪林,羅 興,曾 銘
(四川省醫(yī)學(xué)科學(xué)院·四川省人民醫(yī)院腫瘤中心,四川 成都 610072)
目的比較低劑量放療與高劑量放療在老年局部晚期喉及下咽鱗癌(Locally Advanced Squamous Cell Carcinoma of Larynx or Hypopharynx,LA-SCCL/H)中的療效。方法回顧性分析2011年1月至2015年12月于我院治療的資料完整的LA-SCCL/H患者202例,依據(jù)患者放療劑量是否大于5000 cGy將患者分為低劑量放療組(≤5000cGy)和高劑量放療組(>5000 cGy)。分析兩組患者臨床病理特征與放療劑量的相關(guān)性、總生存時(shí)間及影響LA-SCCL/H患者預(yù)后的因素。結(jié)果年齡、性別、T分期、N分期、原發(fā)灶位置、ECOG評分、居住環(huán)境、吸煙、飲酒及是否違背醫(yī)囑是影響患者放療劑量耐受的因素。在給予同期化療基礎(chǔ)上,高劑量放療組較低劑量放療組總生存期未見延長。單因素及多因素分析發(fā)現(xiàn),年齡、T分期、原發(fā)灶位置、ECOG評分、是否獨(dú)居、飲酒及是否違背醫(yī)囑是影響患者總生存的因素(均P< 0.05),而放療劑量與患者的預(yù)后無明顯相關(guān)性(P>0.05)。結(jié)論低劑量放療在LA-SCCL/H老年患者中具有較好的生存獲益。
低劑量放療;局部晚期喉及下咽鱗癌;療效
隨著人口老齡化,老年人的患癌風(fēng)險(xiǎn)也隨之升高,頭頸部惡性腫瘤是其中之一[1]。據(jù)估計(jì),在這部分老年人群中,局部晚期喉及下咽鱗癌(Locally advanced squamous cell carcinoma of larynx or hypopharynx,LA-SCCL/H)的患病率約為5/10000,但目前相關(guān)的治療指南或規(guī)范相對較少[4]。因此,對于老年LA-SCCL/H患者而言,其治療很大程度上依賴于醫(yī)生及患者的意愿[2]。對于非轉(zhuǎn)移性的老年LA-SCCL/H而言,多數(shù)治療方式為放療和/或加化療,這也是低于75歲患者的標(biāo)準(zhǔn)治療方案[5]??紤]到老年人耐受性以及治療相關(guān)并發(fā)癥,不是所有老年患者都能完成整個(gè)治療過程[10],部分老年患者僅能完成單一的治療方案[12]。自發(fā)現(xiàn)P16陽性的頭頸部腫瘤患者有更好的生存獲益以來,低劑量放療已成為臨床醫(yī)生關(guān)注的焦點(diǎn)[16]。但是,放射腫瘤學(xué)委員會(huì)對于低劑量放療在老年患者中的應(yīng)用卻未達(dá)成共識[8]。本研究擬通過回顧性分析2011年1月至2015年12月于我院治療的LA-SCCL/H患者,了解放療劑量與老年LA-SCCL/H患者生存率的關(guān)系及影響其預(yù)后的因素。
1.1一般資料回顧分析從2011年1月至2015年12月于我院治療的資料完整的LA-SCCL/H患者202例,其中下咽癌77例,喉癌125例,男176例,女26例。納入標(biāo)準(zhǔn):①再次病理復(fù)核證實(shí)為下咽鱗癌或喉鱗癌;②患者年齡>74歲;③T分期為T3~T4;N分期為N0~3;④同時(shí)接受放療及以鉑類為主的化療。排除標(biāo)準(zhǔn);①常規(guī)放療次數(shù)<10次,劑量<3000 cGy;②未完成放療;③非鱗癌患者;④年齡≤74歲;⑤分期為T1或T2期;⑥ECOG評分≥3分;⑦無組織活檢、臨床分期不明確、有遠(yuǎn)處轉(zhuǎn)移;⑧既往有惡性腫瘤病史;⑨治療記錄不完整的患者。⑩僅接受放射治療的患者。依據(jù)患者放療劑量是否大于5000 cGy將患者分為低劑量放療組(≤5000 cGy)和高劑量放療組(>5000 cGy)。兩組患者的中位放療劑量分別是4389 cGy(3000~5000 cGy)及6091 cGy(5010~6600 cGy)。
1.2隨訪所有患者出院后都進(jìn)行了隨訪,主要以電話和門診進(jìn)行隨訪,隨訪內(nèi)容包括一般情況、臨床癥狀及影像學(xué)檢查(頭頸部CT、淺表淋巴結(jié)彩超)。隨訪17~87個(gè)月,中位隨訪時(shí)間是26個(gè)月,隨訪截止日期為2017年5月1日,無失訪患者。
1.3觀察指標(biāo)觀察患者的年齡、性別、T/N分期、PS評分、種族、居住環(huán)境、吸煙史、飲酒史、因違反醫(yī)囑(AMA)而導(dǎo)致的放療停止、獨(dú)居還是和與子女居住等因素對療效及預(yù)后的影響;患者的放療總劑量;患者總生存期(OS)。分析年齡、性別、T分期、N分期、AJCC分期、腫瘤的位置、ECOG評分、居住地、煙酒史、是否獨(dú)居、AMA等與患者放療劑量的相關(guān)性及不同放療劑量對患者預(yù)后的影響。
1.4統(tǒng)計(jì)學(xué)方法數(shù)據(jù)采用SPSS 13.0進(jìn)行分析。計(jì)數(shù)資料的比較采用χ2檢驗(yàn);Kaplan-Meier法繪制生存曲線,并進(jìn)行l(wèi)og-rank檢驗(yàn);多因素Logistic回歸分析影響LA-SCCL/H患者預(yù)后的因素。P< 0.05為差異有統(tǒng)計(jì)學(xué)意義。
2.1患者一般特征202例LA-SCCL/H患者中,159例(78%)患者年齡小于80歲,43例(22%)患者年齡大于80歲。小于80歲組的中位年齡是77歲(75~79歲),而大于80歲組的中位年齡是82歲(80~89歲)。入組患者男女比是8∶1,(176∶26),喉癌/下咽癌比例為1.6∶1(125∶77,P= 0.001)。其中ECOG評分為0或1的比例是93%,吸煙患者與不吸煙患者的比例為2.5∶1(P≤0.001)。飲酒者與非飲酒者的比例為4.1∶1(P=0.014)。
2.2兩組患者臨床病理特征的差異兩組年齡、性別、T分期、N分期、原發(fā)灶位置、ECOG評分、居住環(huán)境、吸煙、飲酒及是否違背醫(yī)囑方面,差異有統(tǒng)計(jì)學(xué)意義(均P<0.05)。而與患者AJCC分期、是否獨(dú)居無關(guān)(P均>0.05,見表1)。而高劑量組中AMA比例遠(yuǎn)高于低劑量組(P= 0.02),這一現(xiàn)象也表現(xiàn)在非獨(dú)居人群及獨(dú)居人群中(P= 0.02)。,IV期/III期,差異無統(tǒng)計(jì)學(xué)意義(P= 0.537);漢族與非漢族間差異無統(tǒng)計(jì)學(xué)意義(P= 0.087)。見表1。
表1 兩組患者臨床病理特征的差異 [n(%)]
AJCC.American Joint Committee on Cancer
2.2不同放療劑量對患者總生存時(shí)間的影響低劑量組患者的中位總生存時(shí)間為(13.95±1.23)月;高劑量組患者的中位總生存時(shí)間為(16.07±1.85)月,組間差異無統(tǒng)計(jì)學(xué)意義(χ2=2.587,P= 0.108)見圖1。
2.3患者總生存時(shí)間(OS)的影響因素多因素Logistic回歸分析結(jié)果顯示年齡、T分期、原發(fā)灶位置、ECOG評分、是否獨(dú)居、飲酒及是否違背醫(yī)囑是影響患者總生存的因素(P均<0.05)。而放療劑量與患者的預(yù)后無明顯相關(guān)性(P>0.05),見表2。
圖1 不同放療劑量對患者總生存時(shí)間的影響
影響因素βSEWaldχ2POR95%CI放療劑量1.0890.1320.6750.43511.000~1.001年齡(歲)0.784-0.7659.503<0.0011.0651.029~1.972性別-0.0140.0092.1690.8560.9560.585~1.561T分期0.0180.0069.489<0.0012.211.513-3.299N分期-00.250.0082.1690.1610.8950.766~1.045原發(fā)灶位置1.1690.4306.9290.0081.5741.123~2.204ECOG評分0.0900.0552.8900.0163.1031.872~11.039民族-0.0010.0020.3880.5390.6260.079~4.937居住環(huán)境0.0000.0001.1020.3500.8580.639~1.105吸煙史0.0910.0532.8930.2071.3750.837~2.279飲酒史0.7550.2449.5720.0050.3980.216~0.736違背醫(yī)囑-0.3270.1773.3960.0131.4781.083~2.016是否獨(dú)居1.1550.4327.151<0.0012.0721.375~3.121
在頭頸部腫瘤治療手段的選擇上,既要考慮盡最大可能地提高腫瘤局部區(qū)域的控制率,又要盡量降低治療對器官功能的損害程度[15]。老年晚期下咽癌及喉癌放化療能更好的保證喉及下咽等器官解剖結(jié)構(gòu)的完整性,但老年患者對放療引起的口腔黏膜反應(yīng)耐受性差,難以耐受整個(gè)放化療治療療程。目前有學(xué)者提出對于局部晚期頭頸部鱗癌患者給予低劑量放療,但成人頭頸部鱗癌低劑量放療的應(yīng)用仍有爭議[17]。Andrew指出一旦放療劑量大于5000 cGy,在任何聲門上型腫瘤中都不會(huì)有生存上的獲益[3]。Nancy和其他學(xué)者已經(jīng)努力降低了HPV(+)患者的放療劑量,其結(jié)果證實(shí)這有利于降低放療毒性[9]。一項(xiàng)中位隨訪時(shí)間為23.3個(gè)月的研究分析顯示:62例(78%)患者在化療顯示CR后接受了5400 cGy的低劑量IMRT聯(lián)合西妥昔單抗,結(jié)果顯示84%患者的PFS為23個(gè)月[13]。本研究通過回顧性分析2011年1月至2015年12月于我院治療的資料完整的LA-SCCL/H患者202例,依據(jù)患者放療劑量是否大于5000 cGy將患者分為低劑量放療組(≤5000 cGy)和高劑量放療組(>5000 cGy)。比較低劑量放療與高劑量放療在老年局部晚期喉及下咽鱗癌中的療效。分析兩組患者臨床病理特征與放療劑量的相關(guān)性、總生存時(shí)間及影響LA-SCCL/H患者預(yù)后的因素。結(jié)果發(fā)現(xiàn)患者的年齡、原發(fā)灶位置、T分期、PS評分、飲酒史、AMA、是否獨(dú)居是影響患者預(yù)后的因素。同時(shí)我們也發(fā)現(xiàn)針對74歲以上的老年人群,在給予同期化療基礎(chǔ)上放療劑量大于5000 cGy組較小于5000 cGy組,其總生存期未見延長。我們推測可能有以下兩方面原因:①與放療毒性和年齡相關(guān)。大于5000 cGy的放療劑量往往會(huì)導(dǎo)致較嚴(yán)重的局部毒性[7],例如嚴(yán)重的急性反應(yīng)(3~4級黏膜炎)及嚴(yán)重的遲發(fā)性反應(yīng)(軟組織纖維化及依賴性經(jīng)皮胃造瘺管,PEG),相關(guān)文獻(xiàn)顯示較高的放療劑量往往導(dǎo)致嚴(yán)重的放療毒副反應(yīng)。據(jù)Lee關(guān)于LA-SCCL/H的報(bào)道,即使有意識進(jìn)行了相關(guān)的預(yù)處理,也有高達(dá)31%的患者長期依賴PEG[11]。長期依賴PEG的原因是因?yàn)楦邉┝糠暖煂?dǎo)致咽食管狹窄、吞咽困難及疼痛[6]。②嚴(yán)重的毒性反應(yīng)和治療密切相關(guān)。研究過程中,我們排除了高PS評分的患者,但是低PS評分并不能作為預(yù)測患者耐受性指標(biāo)[14]。相同的PS也不能表示老年患者生理狀況相同。在有隱匿疾病的老年患者中相同的PS評分可能也沒有使他們從高劑量放療中的獲益得以表現(xiàn)出來。本研究結(jié)果提示低劑量放療在局部晚期喉及下咽鱗癌老年患者中的取得了較好的生存獲益。由于本研究是一個(gè)回顧性的研究,樣本量小,許多數(shù)據(jù)尚不完善(包括化療方案、P16狀態(tài)、PET或MRI影像等),因此尚需擴(kuò)大樣本量進(jìn)一步研究。
另外,由于醫(yī)療記錄僅僅表明了同步放化療,這就導(dǎo)致了我們沒有足夠數(shù)據(jù)區(qū)分是同步放化療還是序貫放化療以及進(jìn)一步明確化療方案及劑量。同時(shí)放化療目的是治療性的還是姑息性的也并未進(jìn)一步納入數(shù)據(jù)統(tǒng)計(jì)。由于缺乏相關(guān)的數(shù)據(jù),所以局部控制情況及無病生存期(DFS)也未納入統(tǒng)計(jì)。
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Effectoflow-doseradiotherapyonlocallyadvancedsquamouscellcarcinomaoflarynxorhypopharynxinelderpatients
HUHong-lin,LUOXin,ZENGMing
(CenterofOncology,SichuanAcademyofMedicalSciences&SichuanProvincialPeople’sHospital,Chengdu610072,China)
ZENGMing
ObjectiveTo compare the effects of the low-dose radiotherapy with high-dose radiotherapy in elder patient with locally advanced laryngeal or hypopharyngeal squamous cell carcinoma (LA-SCCL/H).MethodsWe retrospectively analyzed 202 patients with LA-SCCL/H from January 2011 to December 2015 in our hospital.The patients were divided into low-dose radiotherapy group (5000cGy) and high-dose radiotherapy group (>5000cGy) according to the patient's radiation dose whether is greater than 5000cGy.The correlation between the clinical pathological features and the dose of radiotherapy and between the overall survival time and the prognostic factors were analyzed in the two groups.ResultsAge, gender, T stage, N stage, primary tumor location, ECOG score, living environment, smoking, drinking and whether against medical advice were the influence factors for radiotherapy in patients with dose tolerance.Based on chemotherapy, the total survival period was not prolonged in the high-dose radiotherapy group when compared with the low-dose radiotherapy group.Univariate and multivariate analyses showed that age, T stage, location of primary lesion, ECOG score, whether or not to live alone, alcohol consumption, and compliance with physician order were the factors influencing overall survival (allP< 0.05).There was no significant correlation between the dose of radiotherapy and the prognosis of patients (P> 0.05).ConclusionLow-dose radiation therapy has a better survival benefit in elderly patients with LA-SCCL/H.
Low dose radiotherapy;Locally Advanced Squamous Cell Carcinoma of Larynx or Hypopharynx;Effect
曾 銘
R739.8
A
1672-6170(2017)05-0216-05
2017-02-25;
2017-07-23)