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《中国恶性肿瘤学科发展报告(2023)》——胃癌研究进展篇
2024-04-30 17:40

 

概述

胃癌是中国最常见的恶性肿瘤之一,发病率和死亡率均高居我国第三位[1]。我国胃癌患者具有分期晚、肿瘤负荷大等特点,胃癌防治工作任重道远。2022年,胃癌研究取得多方面进展,包括诊断手段、治疗策略、转化研究等方面。本文拟总结2022-2023年国内外胃癌研究结果,为未来临床研究的深入开展、临床实践的方案制定提供思路和建议。

01

胃癌免疫治疗进展

CheckMate-649、ORIENT-16、KEYNOTE-811等多项临床研究数据为晚期胃癌一线免疫治疗提供了坚实证据。CheckMate-649中国亚组3年随访数据显示[2],接受Nivolumab治疗患者的中位PFS较化疗组延长近1.5倍;其中CPS≥5人群的中位PFS延长近2倍,3年OS率可达31%,是化疗组的近3倍。同样ORIENT-16[3]的长期随访数据显示信迪利单抗联合化疗显著降低CPS≥5人群和总体人群的死亡风险,且总体治疗安全性良好。上述研究结果奠定了免疫治疗在中国胃癌一线治疗的标准地位。2023年胃癌免疫治疗主要研究方向如下:

1.1 晚期胃癌一线联合免疫治疗选择增加

GEMSTONE-303研究[4]精准筛选人群,与安慰剂联合化疗相比,舒格利单抗联合化疗组在PD-L1表达≥5%人群中显著改善了PFS(7.62m vs 6.08m)和OS(15.64m vs 12.65m),且ORR提高了15.9%(68.6% vs 52.7%);在PD-L1表达≥10%人群中获益更明显。舒格利单抗也成为全球首个在胃癌领域取得成功的PD-L1抑制剂。RATIONALE-305研究[5]显示替雷利珠单抗联合化疗能显著延长PD-L1肿瘤区域阳性评分(TAP)≥5%患者的中位OS(17.2m vs 12.6m)和中位PFS(7.2m vs 5.9m),并可提高患者ORR(50.4% vs 43%)和中位DOR(9.0m vs 7.1m)。KEYNOTE-859研究[6]显示化疗联合帕博利珠单抗在总人群和CPS≥1人群中OS可延长1.5m和1.6m,在CPS≥10的人群中OS延长近4个月。以上研究结果提供了多种晚期胃癌一线免疫联合化疗方案,其中PD-L1表达越高的患者OS获益趋势越明显。

1.2 双免治疗有望进一步扩大免疫治疗获益人群  

卡度尼利单抗(AK104)是全球首个进入临床试验的PD-1/CTLA-4双特异抗体。2023年更新了卡度尼利单抗联合化疗用于胃癌一线Ib/Ⅱ期临床研究的2年随访数据[7],结果显示联合治疗组全人群中位OS时间达17.41个月,中位PFS达9.2个月,12个月OS率为61.4%,ORR达68.2%,DCR达92%;在PD-L1 CPS≥5人群中,中位OS时间高达20.24个月。其中该试验入组的PD-L1表达阴性(CPS<1)人群占比>50%,亚组分析中,PD-L1 CPS<1人群中位OS时间达17.64个月,中位PFS时间为8.18个月。提示卡度尼利单抗联合化疗在PD-L1低表达或阴性患者中仍体现出卓著的疗效。期待后续III期研究相关数据的公开。

1.3 免疫治疗向局部进展期胃癌推进

2023年ASCO报告多项胃癌围手术期联合免疫治疗的II期研究结果,如特瑞普利单抗[8]、信迪利单抗[9]等均观察到了pCR率的明显提升。DANTE研究[10]中,阿替利珠单抗联合FLOT治疗在病理降期和病理缓解上均观察到明显获益。III期MATTERHORN研究[11]中,度伐利尤单抗联合FLOT治疗同样改善了患者的pCR率(19% vs 7%),但长期生存数据仍有待进一步更新。KEYNOTE-585研究[12]是首个报道生存随访数据的胃癌围手术期全球III期临床试验,该研究设置两个主要终点,分别为pCR率和EFS;结果显示与单纯化疗相比,联合帕博利珠单抗显著提升pCR率(12.9% vs 2%);并在数值上延长了EFS(44.4m vs 25.3m),但无统计学意义;主要队列中两组的生存曲线也紧密交叉(HR 0.90),但亚组分析中MSI-H患者的OS获益明显(HR 0.38)。该研究进一步夯实了与化疗时代相比,添加免疫检查点抑制剂可使pCR率提升约10%,但短期疗效pCR率的改善能否转化为长期生存,仍有待进一步探索。

ATTRACTION-5研究[13]首次探索了胃癌辅助治疗中联合nivolumab的疗效和安全性,结果提示nivolumab +化疗组和安慰剂+化疗组的3年RFS率分别为68.4%和65.3%,虽然整体为阴性结果,但亚组分析显示对于TPS≥1%的胃癌患者,联合免疫联合获益显著,未来仍需要进一步探索获益人群。

此外包含抗血管生成药物的联合治疗方案也开始进入围手术期探索。Dragon-IV/Ahead-G208研究[14]结果提示,阿帕替尼+卡瑞利珠单抗+SOX化疗方案组的pCR率为18.3%,而单纯化疗组为5%。另一项Ⅱ期研究结果[15]显示局晚期(cT4a/bN+)胃癌患者,围手术期使用卡瑞利珠单抗+阿帕替尼+S-1联合或不联合奥沙利铂的pCR分别为15.8%和26.3%。多组学分析揭示了几种潜在的生物标志物,包括RREB1和SSPO突变、免疫相关特征和外周T细胞扩增评分,并探索了新辅助免疫治疗期间免疫微环境、显性肿瘤亚克隆和T细胞受体库的动态变化。这些数据有待在大型随机试验中进一步验证。

1.4 特殊人群的精准免疫治疗探索

作为胃癌中的特殊亚型,MSI-H胃癌历来被看作免疫治疗的优势人群。围手术期治疗中,GERCOR NEONIPIGA[16]及INFNITY[17]研究结果显示MSI-H胃癌患者经PD-1、PD-L1抑制剂联合CTLA-4的双免治疗后的pCR率分别达59%、60%,证实了双免治疗在MSI-H胃癌患者治疗中带来了强有力的抗肿瘤疗效。但上述研究中前者入组患者临床分期偏早,后者T4患者pCR率仅17%,而T2~3期患者pCR率近90%,双免疗法的稳定性仍有待更大样本验证。

晚期治疗中,KEYNOTE-061、KEYNOTE-062研究结果已经初步提示了免疫治疗在MSI-H胃癌中的高应答率。2023年ESMO年度会议上报道了KEYNOTE-158研究中国队列结果[18],其ORR达70%,12个月的DOR率高达85.7%,再次印证了帕博利珠单抗在中国晚期MSI-H实体瘤患者中持久的抗肿瘤活性。MSI-H胃癌双免治疗模式探索也在持续进行中。NO LIMIT研究[19]初步结果显示,纳武利尤联合伊匹木单抗用于一线治疗进展期胃癌和MSI-H胃食管结合部癌患者的ORR为62.1%,其中3例患者(10%)达CR,DCR为79.3%,中位PFS时间为13.8个月;安全性方面,与已知的双免治疗安全谱一致。在CheckMate 649生物标志物分析中[20],Treg细胞比例高、趋化因子多、成纤维细胞和内皮细胞比例低均与双免治疗患者更长久的生存有关。这些生物标志物的临床效用有待进一步前瞻性验证。

02

胃癌靶向治疗进展

2.1 HER2阳性胃癌化靶免联合治疗策略不断更新

KEYNOTE-811研究一线对比曲妥珠单抗+化疗联合或不联合帕博利珠单抗治疗HER2阳性晚期胃癌的疗效,第3次中期分期(随访至38.5m)结果[21]显示,帕博利珠单抗联合方案组中位OS为20.0m,靶向联合化疗组中位OS为16.8m(HR=0.84),未达到OS时间显著延长的主要终点;亚组分析中显示 CPS<1的患者帕博利珠单抗联合治疗组的PFS时间与对照组相近(9.5m vs 9.5m,HR=1.03),OS时间甚至劣于对照组(16.1m vs 22.3m,HR=1.61),其中机制有待进一步挖掘。

泽尼达妥单抗是一种双特异性抗体,可同时靶向HER2的两个非重叠表位。泽尼达妥单抗联合替雷利珠单抗和化疗一线治疗HER2阳性晚期胃癌患者的Ⅰb/Ⅱ期研究中,总人群ORR达75.8%,DCR为100%;中位PFS时间为16.7m,mDOR达22.8m。这提示泽尼达妥单抗联合化疗和免疫治疗的组合疗法有望产生显著、持续的疗效[22]。此外,卡瑞利珠单抗联合吡咯替尼和化疗在HER2阳性胃癌一线治疗的I期研究中显示出良好的疗效,ORR和DCR分别为96.0%和100%[23]。吡咯替尼联合SHR6390在晚期HER2阳性胃癌或实体瘤中的ORR和DCR分别为50.0%和93.8%,中位PFS时间为3.88m,中位OS时间为12.48m [24]。这显示出了鼓舞人心的疗效。

2.2 HER2 ADC药物研究蓬勃发展

基于国产药物维迪西妥单抗用于三线及以上HER2阳性胃癌患者的阳性研究结果,国内个别指南更新了HER2阳性胃癌的三线靶向治疗方案,将维迪西妥单抗由Ⅱ级推荐前移至Ⅰ级推荐。DESTINY-Gastric06研究[25]评估了DS-8201单药治疗接受过≥二线治疗的中国HER2阳性晚期胃癌患者的有效性和安全性,其中患者ORR为28.8%,中位OS、PFS时间和mDOR分别为10.2个月、5.7个月和7.9个月;整体安全性可控,发生药物相关的间质性肺病的患者共3例(3.2%),其中2例为1级,1例为2级。DS-8201有望为我国HER2阳性晚期患者群体提供了更为有效的个体化治疗方案。

2.3 Claudin18.2蛋白靶点研究进展

SPOTLIGHT[26]和GLOW[27]两项Ⅲ期研究分别评估了佐妥昔单抗联合mFOLFOX6或XELOX方案治疗CLDN18.2阳性、HER2阴性晚期胃癌的疗效和安全性,均显示出PFS、OS的显著延长,证实了靶向CLDN18.2治疗的巨大潜力。TST001[28]、ZL-1121[29]、MIL93[30]、Q-1802[31]研究中单抗、双抗药物的初步结果也为CLDN18.2这一靶点增加了依据。

随着ADC技术的不断革新,CLDN18.2的ADC药物探索与创新也在蓬勃发展。SYSA1801在CLDN18.2表达晚期恶性实体瘤患者中已显现出良好的早期抗肿瘤疗效[32],CMG901等Ⅰ期研究也初步展露成果[33]。探索CLDN18.2 ADC药物与免疫治疗的联合探索也成为未来的热点方向,相关临床研究均在进行中。

2.4 其他靶点研究进展

除HER-2和Claudin18.2之外,胃癌的靶向治疗已经进展到多靶点时代。FGFR2也可能是治疗胃癌的一种新靶点,相关治疗药物崭露头角。Bemarituzumab联合化疗可延长FGFR2b过表达、HER2阴性胃癌患者生存期,降低疾病进展或死亡风险,且安全性可接受[34]。Futibatinib单药治疗FGFR2扩增胃癌展现出显著的抗肿瘤活性和可控的安全性,ORR可达17.9%,中位PFS和OS分别为2.8个月和5.7个月[35]。相关的临床研究、治疗方案等仍需要进一步探索。cMET、TROP2、DKK1等新靶点相关临床研究仍在不断开展,精准靶向治疗已成为未来药物研究的必然方向,期待更多的阳性结果。

03

胃癌外科治疗进展

3.1 腹腔镜全胃对比腹腔镜近端胃双通道的临床疗效

韩国KLASS?05研究比较分析了腹腔镜近端胃切除(LTG) +双通道吻合(DTR)(LPG+DTR)及腹腔镜全胃切除术(LTG)的临床疗效[36],研究纳入了68例LPG+DTR患者和69例LTG患者,结果表明两组在并发症发生率(17.6% vs 10.1%,P=0.31)、食管反流率(2.9% vs 2.9%, P=0.9)、术后2年血红蛋白的下降值(-6.9% vs -5.6%, P=0.35)、术后2年的总生存率(98.5% vs 100%, P=0.33)以及无病生成率(98.5% vs 97.1%; P=0.54)的差异均无统计学意义。但是,LPG+DTR术后维生素B12的补充量显著低于LTG [0.4mg vs 2.5mg, (95% CI, 1.3-2.9 mg; P < 0.001) ]。

3.2 单孔对比多孔腹腔镜胃癌根治术对胃癌患者临床疗效及生活质量的影响

韩国2023年的一项RCT研究纳入43名单孔腹腔镜远端胃癌根治术(SIDG)患者和40名多孔腹腔镜远端胃癌根治术(MLDG)组患者[37]。结果表明,MLDG组和SIDG组的平均手术时间(154.3±53.3 min vs 148.9±50.1 min,P=0.631)、疼痛评分(MLDG = 4.0±1.3,SIDG = 4.3±1.3,P=0.372)、平均住院时间(5.5 days vs 5 days, P=0.993)以及术后生活质量评分(QoL)评分差异均无统计学意义。

3.3 细胞减灭术联合腹腔热灌注化疗治疗胃癌腹膜转移患者的效果

腹腔热灌注化疗(HIPEC)是一种腹腔恶性肿瘤辅助治疗手段。2023年10月,德国Beate  Rau等作者发布了GASTRIPEC-I III期研究结果[38],该研究评估细胞减灭术(CRS)后接受腹腔热灌注化疗(HIPEC)对腹膜转移胃癌患者总生存率的影响。初治的胃癌腹膜转移的患者被随机分配到单独的 CRS 组(CRS-A)或组CRS联合HIPEC(CRS+H)组。计划入组180名患者,因入组缓慢,入组105 名患者后停止招募患者。其中52 名接受 CRS+H,53 名接受 CRS-A。相较CRS-A,CRS+H可显著改善患者无进展生存期(PFS)(7.1 months vs 3.5 months,P=0.0472)、远处转移生存期(MFS)(10.2 months vs 9.2 months,P=0.0286)。然而在总生存期(OS)两组无显著差异(14.9 months vs 14.9 months,P=0.1647)。

3.4 机器人胃癌手术进展

机器人胃癌手术以其微创性和精准性等特点逐渐成为胃癌治疗的重要手段。美国学者Felipe B. Maegawa等通过对2010至2019年间美国国家癌症数据库中的11173例胃癌微创手术病例进行分析[39],研究对比了机器人手术与腹腔镜手术在胃癌根治性手术中的疗效。研究发现,在非配对的队列中,相较于腹腔镜手术组,机器人手术组具有更高的16枚以上淋巴结清扫率(63.5 vs 57.1%,P < 0.0001)及阴性切缘率(93.8% vs 91.9%,P < 0.001),具有更低的延长住院率(26.0% vs 29.6%,P<0.001)、术后90天死亡率(3.7% vs 5.0%,P<0.0001)及5年生存率(56% vs 54%,P=0.03)。但是在进行了倾向性得分匹配后的分析显示,机器人手术仅在16枚以上淋巴结清扫率方面优于腹腔镜(63.5% vs 60.4%,P=0.01)。此外,在一项涵盖25521例病例的系统回顾和Meta分析研究显示[40],机器人与腹腔镜手术在开腹中转率、再手术率、死亡率、总体并发症发生率、吻合口瘘、切缘阳性率以及肿瘤复发率等方面的差异均无统计学意义。但是,在失血量(mean difference [MD]:19.43 mL, P<0.00001)、住院时间(MD: 0.50天, P=0.0007)、首次排气时间(MD: 0.52 days, P<0.00001)、术后进食时间(MD: 0.17 days, P=0.0001)、淋巴结清扫数(MD: 1.69, P=0.001)、III级以上并发症发生率(RR=0.68, P<0.0001)和胰瘘发生率(RR=0.51, P=0.007)方面,机器人手术显著优于腹腔镜。然而,相较于腹腔镜手术,机器人手术时间明显较长(MD:41.19 min, P<0.00001),并且费用也显著较高(MD:3684.27 U.S. Dollars, P<0.00001)。

3.5 腹腔镜下保脾的脾门淋巴结清扫术在局部进展期近端胃癌治疗中的研究

黄昌明教授团队的一项前瞻性III期随机对照临床试验,评估了腹腔镜下保脾的脾门淋巴结清扫术在局部进展期近端胃癌治疗中的效果[41]。该研究结果表明对于非侵犯大弯侧的进展期胃上部癌,相较于传统的D2淋巴结清扫,行腹腔镜保脾的脾门淋巴结清扫(D2+No.10)是安全可行的,并且腹腔镜保脾的脾门淋巴结清扫能显著提高患者的3年总生存率(75.7% [95% CI, 70.6-80.8] vs 66.5% [95% CI, 60.8-72.2],P=0.02)。

04

 胃癌内镜治疗进展

内镜治疗适用于淋巴结转移可能性极低的EGC,包括内镜下黏膜切除术(endoscopic mucosal resection,EMR)和内镜下黏膜剥离术(endoscopic submucosal dissection,ESD)。绝对适应证:1)无合并溃疡的分化型黏膜内癌(cT1a);2)病灶大小≤3 cm、有溃疡的分化型黏膜内癌(cT1a);3)胃黏膜高级别上皮内瘤变(HGIN)。扩大适应证:病灶大小≤2 cm、无溃疡的未分化型黏膜内癌(cT1a)。对不符合上述适应证,但手术风险较大,可将内镜切除作为相对适应证,应注意肿瘤残留及淋巴结转移风险。禁忌证:1)存在淋巴结转移;2)肿瘤侵犯固有肌层;3)不可耐受内镜下切除。内镜切除后局部复发者行内镜二次切除尚存争议。内镜下切除的根治度由局部切除程度和淋巴结转移可能性决定,推荐采用eCura系统进行评价。eCuraA及eCuraB者定期随访即可。而eCuraC-1发生淋巴结转移的风险低,可选择再行ESD或追加外科切除;当出现在黏膜下浸润部分或断端阳性时,应追加外科切除。对于eCuraC-2者原则上应追加外科切除。ESD分类为高出血风险的手术,并建议在进行ESD 时,对于服用单抗、双抗患者采用以下治疗方案:阿司匹林中断治疗3至5天,吩并吡啶中断治疗5至7天,其他药物中断1天预约安排[42]。建议即使在治愈性 ESD 之后,也需要持续监测5年内窥镜检查以识别第二胃癌[43]。对晚期老年患者(75岁)进行 EGC 的 ER 可能会提高预期寿命[44]。推荐 ER 用于 一般状态及营养良好且预期 ER 为非 eCura C-2 的患者[45]。 使用 AI辅助有助于早期胃癌诊断[46]。

05

胃癌基础和转化研究进展

5.1 胃癌基础研究进展

揭示胃癌转移相关分子机制及相关治疗策略:通过胃癌恶性腹水建立类器官模型进行检测,结果显示抑制WNT信号通路可降低腹水上清的促进生长功能,提示WNT信号通路是胃癌腹膜转移的潜在治疗目标 [47];一项研究显示肿瘤相关成纤维细胞(CAFs)产生的SLIT2蛋白可以通过与ROBO1结合促进胃癌转移,并且可以通过增加CTTN的表达和磷酸化水平,诱导细胞骨架重组,使肿瘤细胞获得过度的迁移能力,参与这一过程的关键分子有可能成为探索胃癌转移的潜在生物标志物和治疗靶点[48]。挖掘胃癌发生发展过程中的肿瘤微环境(TME)特点:一项研究分别对胃癌癌前病变、局限期以及转移性胃癌进行单细胞分析,通过识别TME中细胞状态和成分改变绘制了一个高分辨率的胃癌TME图集,并提供了潜在研究靶点 [49];研究发现抗PD-1和抗Dectin-1抗体的联合治疗在促进CD8+T细胞增殖和肿瘤细胞凋亡方面起到了协同效应,提示阻断Dectin-1可能提供一种新的治疗方法,扩大了靶向肿瘤相关巨噬细胞(TAM)的治疗范围 [50]。另有研究发现circSLC4A7增加了类似肿瘤干细胞的特性,并促进了胃癌细胞的增殖、迁移和入侵[51];EBV状态对胃癌治疗及免疫反应的影响:EBV(+)GC免疫反应强,T细胞活跃,免疫微环境与EBV(-)GC存在显著差异,且和胃癌免疫治疗的疗效存在一定相关性[52]。

5.2 胃癌转化研究进展

发现胃癌潜在治疗靶点:铁死亡相关ACTL6A[53]、针对不良预后SLC39A10基因的靶点CK2[54]、RNA干扰策略潜在靶点NR_033928[55]、肿瘤相关成纤维细胞SDC2[56]、与抗血管生成治疗耐药相关的mRNA ac4C修饰等。构建了识别胃癌风险的临床和分子模型,以及针对不同人群推荐的早筛策略,为胃癌的精准预防提供了机会[57]。另外,人工智能技术(AI)突飞猛进发展,中国学者研究了舌象与胃癌的关系并结合AI开发了基于舌象的胃癌诊断新技术,诊断价值突出,且与血液肿瘤指标的融合可以进一步提高其诊断价值[58]。

06

胃癌影像学研究进展

6.1 胃癌影像学分期及风险度评价

Liu等[59]开发基于胃癌术前 CT 和临床数据的多模态(CT/EHRs)人工智能模型,纳入602例胃癌患者、提取1316个影像组学特征及10个EHRs特征,组合输入四个多层感知器自动学习神经架构搜索策略(NAS),预测TN分期的效能优于传统手段。Luo等[60]结合能谱CT 70keV 动脉期 CT 值、静脉期电子密度和簇状分布特征预测淋巴结转移,AUC值达到0.855-0.907。Sun等[61]基于2005例胃癌瘤内及瘤周CT影像组学特征构建模型,辅助临床医生对腹膜转移诊断的准确率提高10%-20%。Li 等[62]开发基于能谱CT 的诺模图术前预测局部进展期胃癌神经浸润,实验和验证队列 AUC分别达到 0.853和0.782,高于其他预测指标。

6.2 胃癌治疗疗效评估

Wei等[63]根据肿瘤厚度缩小率、动脉期原发肿瘤CT值降低率和静脉期最大淋巴结缩小率建立多变量预测模型,预测胃癌新辅助化疗后病理反应的AUC 值达到0.955。Zheng等[64]通过CT影像组学评分预测D2淋巴结清扫术后接受放疗和放化疗的胃癌患者疗效,测试队列中 DFS 和 OS 的 C 指数分别为0.721和0.774。Can等[65]纳入6家医院共1060例局部进展期胃癌病例的基线CT 影像建立深度学习模型,该模型预测患者新辅助化疗疗效的 AUC 为0.82-0.86。Jiang等[66]将免疫组化深度学习模型和放射组学结合构建评估肿瘤微环境(TME)模型,联合 CPS 辅助判断化疗及抗PD-1疗效AUC值达到0.783。Chen等[67]结合临床和病理参数(LVI)构建MRI影像组学联合模型,预测 AGC 患者3年和5年OS的 AUC 值可达0.765和0.788。Li等[68]基于T2WI、ADC值和动态增强以及Borrmann分型建立多参数 MRI影像组学模型,预测胃癌新辅助化疗治疗反应效能良好,预测 OS及PFS的 AUC 值分别为0.844和0.820。

6.3 胃癌预后及生存预测相关研究进展

Wang等[69]基于283名极晚期胃癌患者(cT4a/bNxM0-1)原发灶和腹膜、肝脏、淋巴结转移灶的影像组学征象构建联合模型,能够较好的预测患者PFS,并能对不同转移灶亚组的 PFS 和OS 进行分层。Zhu等[70]基于双层光谱探测器CT(DLCT)和临床放射学特征构建预测模型,为无创预测胃癌MSI状态和术后肿瘤复发风险分层提供了有效的工具。Huang等[71]开发和验证 CT 成像生物标志物,可有效预测胃癌患者的免疫治疗反应,并发现其与先天免疫信号传导相关,可作为个体治疗决策的潜在工具。Yang等[72]探讨CT检测的EMVI相关基因与胃癌患者免疫治疗耐药和免疫逃逸的相关性,发现 CT 检测到的 EMVI 基因特征可能是 ICI 治疗的潜在阴性生物标志物,该特征与 TMB 和 MSI 呈负相关,可预测较差的预后。He等[73]使用深度学习自动分割模型对接受PD-1和HER2联合治疗的晚期胃癌患者进行身体成分分析,发现皮下脂肪面积联合免疫炎症指数与总生存期显著相关。

07

胃癌治疗新技术

人工智能技术和纳米颗粒技术的发展为胃癌早期诊断提供新选择。人工智能算法在消化不良人群中测试胃癌特征具有准确率高、灵敏度高、误报率低、漏报率低的特点,为非侵入性胃癌筛查方法提供新思路[74]。国内研究通过纳米颗粒技术构建胃癌诊断模型,可提高胃癌早诊率和准确性,有望改善早期胃癌人群的预后[75]。Ju-Seog Lee等对先前确定的GAS亚型进行荟萃分析,利用二元载体COCA重新发现了与先前相似的亚型及先前研究未发现的新亚型,揭示了各亚型总生存率和对治疗的潜在反应,为GAC的研究提供了新的信息[76]。液体活检技术可实时检测肿瘤动态变化,进行疗效预测和预后评估,逐步改变了癌症诊治格局。在预后评估方面,研究表明在基线、新辅助化疗后或手术后的II/III期胃癌,ctDNA阴性者预后均优于阳性患者,3年OS可分别高达74%与73%,有望成为 II/III期胃癌预后和新辅助治疗的预测标志物[77]。在评估MRD与胃癌复发方面,CALIBRATE-GC结果证实基于ctDNA的MRD检测可更好实现II/III期胃癌术后、辅助化疗后的复发风险预测[78]。在早期胃癌检出方面, ASCEND-GASTRIC研究结果表明cfDNA甲基化在检测早期胃癌的性能上要优于ctDNA突变或血清肿瘤标志物[79]。

08

胃癌护理研究进展

目前胃癌护理领域研究集中于围手术期干预策略和营养支持方面,包括技术化策略、循证护理、健康教育、精细化护理等。Fan等[80]在胃癌围手术期护理过程中融入中医方法,如中医食疗、穴位推拿,均能有效减少和预防并发症发生,改善生活质量。Zhang[81]等通过对胃癌化疗期患者实施强化认知干预、睡眠疗法、心理干预、用药指导等措施,能有效降低化疗毒副反应对患者身心影响。Wei[82]等以循证护理为基础,整合现有证据制定胃癌患者围手术期集束化护理策略,并应用于临床实践,在胃癌围手术期胃肠功能保护安全性、有效性、可行性方面发挥重要作用。在营养支持方面,主要针对胃癌术后患者ONS摄入依从性影响因素[83]及营养护理对策展开研究。Xu等[84]依据术后预后情况将96例胃癌术后患者分为预后良好组和预后不良组,采用单因素和多因素分析法对胃癌术后预后不良的影响因素进行分析,结果发现,体重指数(BMI)≥28.00 kg/m2,住院时间≥10天,术前并发症≥2个是胃癌术后预后不良独立危险因素。Tong[85]创新性将慢病轨迹模型引入到营养护理管理中,可有效改善胃癌患者营养状况和负面情绪,降低其营养不良发生率。

【主编】

梁   寒   天津医科大学肿瘤医院

【副主编】

黄   华    复旦大学肿瘤医院

肖   莉    厦门大学中山医院

唐   磊    北京大学肿瘤医院

骆卉妍    中山大学肿瘤防治中心

张小田    北京大学肿瘤医院

王雅坤(执笔)北京大学肿瘤医院

【编委】(按姓氏拼音排序)

邓靖宇    天津医科大学肿瘤医院

李   凯    中国医科大学第一医院

臧   潞    上海交通大学瑞金医院

陕   飞    北京大学肿瘤医院

邓   婷    天津医科大学肿瘤医院

季   刚    空军医科大学消化病院

【专家顾问】(审稿专家)

沈   琳    北京大学肿瘤医院

季加孚    北京大学肿瘤医院

李子禹    北京大学肿瘤医院

梁   寒    天津医科大学肿瘤医院

徐惠绵    中国医科大学第一医院

朱正纲    上海交通大学瑞金医院

陈   凛    中国人民解放军总医院

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