外科理论与实践 ›› 2024, Vol. 29 ›› Issue (03): 220-229.doi: 10.16139/j.1007-9610.2024.03.07
收稿日期:
2024-03-25
出版日期:
2024-05-25
发布日期:
2024-09-03
通讯作者:
章真,E-mail:zhen_zhang@fudan.edu.cn基金资助:
WANG Yaqi, XIA Fan, ZHANG Zhen()
Received:
2024-03-25
Online:
2024-05-25
Published:
2024-09-03
摘要:
对于局部进展期直肠癌(LARC),新辅助放化疗联合全直肠系膜切除术(TME)的标准治疗模式肿瘤退缩和保肛率仍有限,且无法降低远处转移率。放疗可促进机体免疫应答,放疗和免疫治疗联合具有良好的协同作用,有望突破微卫星稳定(MSS)型结肠直肠癌的治疗困境。近年来,新辅助放化疗联合免疫治疗的临床试验逐渐展开,大多获得满意的肿瘤完全缓解率,为MSS型中、低位LARC病人保留器官功能提供新的选择。未来仍需更多大样本随机对照研究进行验证,期待获得更好的保肛和远期生存获益。同时在放疗与免疫治疗模式、疗效准确评估等方面需进一步优化和努力。
中图分类号:
王雅琪, 夏凡, 章真. 局部进展期直肠癌新辅助放化疗联合免疫治疗的回顾和展望[J]. 外科理论与实践, 2024, 29(03): 220-229.
WANG Yaqi, XIA Fan, ZHANG Zhen. Review and prospect of neoadjuvant chemoradiotherapy combined with immunotherapy in locally advanced rectal cancer[J]. Journal of Surgery Concepts & Practice, 2024, 29(03): 220-229.
表1
MSS型LARC新辅助放化疗联合免疫治疗临床试验疗效汇总
类别 | 名称/NCT编号 | 年份 | 国家地区 | 期别 | 样本量 | 病人特征 | 研究设计 | CR率(%) |
---|---|---|---|---|---|---|---|---|
长程放 化疗序 贯免疫 治疗 | VOLTAGE-A[ NCT02948348 | 2019 | 日本 | Ⅰb | 37 | Ⅲ期 23% | LCRT+Nivo×5 | 30 |
NSABP FR-2[ NCT03102047 | 2021 | 美国 | Ⅱ | 45 | Ⅲ期 89% | LCRT+Durva×4 | 53 | |
PANDORA[ NCT04083365 | 2021 | 意大利 | Ⅱ | 55 | T3-4 95%; N+ 79% | LCRT+Nivo×3 | 32.7 | |
长程放 化疗同 期免疫 治疗 | AVANA[ NCT03854799 | 2021 | 意大利 | Ⅱ | 101 | Ⅲ期 94% | LCRT/Avelu×6 | 23 |
R-IMMUNE[ NCT03127007 | 2023 | 北美 | Ⅰb/Ⅱ | 37 | Ⅲ期 84% | LCRT/Atezo×4 | 27 | |
NECTAR[ NCT04911517 | 2024 | 中国北京 | Ⅱ | 50 | T3-4 92%; N+ 64% | LCRT/Tisleli×3 | 40 | |
长程放 化疗联 合化疗 免疫 | NRG-GI002[ NCT02921256 | 2021 | 美国 | Ⅱ | 95 | 高危T3-4/N+ | FOLFOX×8+(LCRT+Pembro×6) | 45 |
长海研究[ ChiCTR2100042785 | 2022 | 中国上海 | Ⅱ | 23 | T2-T3; N0 69% | LCRT/Sintili×2+(CAPOX×6+ Sintili×2) | 52.2 | |
PKUCH 04[ NCT04340401 | 2022 | 中国北京 | Ⅱ | 25 | N2 76%; MRF+56% | (CAPOX+ Camreli)×3+LCRT+CAPOX×2 | 49.3 | |
DUREC[ NCT04293419 | 2023 | 西班牙 | Ⅱ | 61 | T3-4/N+ | FOLFOX×6+Durva×6+LCRT | 39 | |
STARS-RC03[ NCT04906044 | 2023 | 中国吉林 | Ⅱ | 30 | T3-4/N+ | TNT/Sintili | 55 | |
短程放 疗序贯 化疗免 疫 | Averectal[ NCT03503630 | 2021 | 欧洲 | Ⅱ | 40 | Ⅲ期 91% | SCRT+(FOLFOX+Avelu)×6 | 37.5 |
武汉协和Ⅱ期[ NCT04231552 | 2021 | 中国湖北 | Ⅱ | 30 | 高危T3-4/N+ | SCRT+(CAPOX+Camreli)×2 | 46 | |
UNION[ NCT04928807 | 2023 | 中国湖北 | Ⅲ | 231 | T3-4/N+ | Arm1: SCRT+(CAPOX+Camreli)×2 Arm2: LCRT+CAPOX×2 | 39.8 vs. 15.3 | |
TORCH[ NCT04518280 | 2023 | 中国上海 | Ⅱ | 130 | T3-4/N+ | Arm1: SCRT+(CAPOX+Toripali)×6 Arm2: (CAPOX+Toripali)×2+SCRT+(CAPOX+Toripali)×4 | 57.4 vs. 54.0 | |
PRECAM[ NCT05216653 | 2023 | 中国浙江 | Ⅱ | 32 | T3-4/N+ | SCRT+ CAPOX×2/Envafo (qw)×6 | 66.7 |
表2
MSS型LARC新辅助放化疗联合免疫治疗正在进行的临床试验基本信息汇总
类别 | 名称/NCT编号 | 年份 | 国家 | 期别 | 样本量 | 患者特征 | 研究设计 | CR |
---|---|---|---|---|---|---|---|---|
长程放化疗 序贯免疫 治疗 | TIMENT-R NCT05507112 | 2022 | 中国北京 | Ⅱ | 100 | T3-4/N+ | Arm1: LCRT+8-12w后Tisleli×3+TME Arm2: LCRT+8-12w后TME | pCR |
Ave-Rec NCT03299660 | 2023 | 澳大利亚 | Ⅱ | 37 | T3b-4/N1-2 | LCRT+Avelu×4 | pCR | |
长程放化疗 同期免疫 治疗 | 北京友谊Ⅲ期 NCT05245474 | 2023 | 中国北京 | Ⅲ | 186 | cT3-4aN0M0 cT1- 4aN1-2M0 | Arm1: LCRT/Tisleli×3 Arm2: LCRT+Tisleli×3 Arm3: LCRT | pCR |
CHINOREC NCT04124601 | 2022 | 奥地利 | Ⅱ | 80 | T3-4/N+ | LCRT/(Ipili×1+Nivo×3) | AEs, mrTRG, pTRG | |
长程放化疗 联合化疗 免疫 | 中山肿瘤研究 NCT04304209 | 2019 | 中国广州 | Ⅱ | 134 | T3-4/N+ | Arm1 ((/Sintili+CAPOX)×4+50Gy)评估后 ①+ TME/WW + CAPOX×4 ②+ CAPOX×4 + TME/WW Arm 2 pMMR:CAPOX×4+50Gy评估后 ①+ TME/WW + CAPOX×4 ②+ CAPOX×4 + TME/WW | CR |
CHOICE Ⅱ NCT05215379 | 2022 | 中国上海 | Ⅱ-Ⅲ | 距肛≤5cm T1-3aN0-1 | Arm1: LCRT+CAPOX×2 Arm2: LCRT/Sintili×2+(CAPOX+ Sintili)×2 | cCR | ||
短程放疗序 贯化疗免疫 | STELLAR Ⅱ NCT05484024 | 2023 | 中国北京 | Ⅲ | 588 | T3-4/N+ | Arm1: SCRT + (CAPOX×4/FOLFOX×6)//Sintili×4 Arm2: SCRT + CAPOX×4/FOLFOX×6 | CR |
浙江肿瘤 NCT04663763 | 2023 | 中国浙江 | Ⅱ | 40 | T3-4/N+ | SCRT + (CAPOX+Sintili)×4 | pCR | |
N-PRC NCT05576480 | 2023 | 中国上海 | Ⅱ | 55 | T3-4/N+ | (SCRT+Penpuli d6/7)+(CAPOX+Penpuli)×4 | pCR | |
PRECAM-R NCT05752136 | 2023 | 中国浙江 | Ⅱ | 32 | T3-4/N+ | Arm1 SCRT+CAPOX×2 Arm2 SCRT+ CAPOX×2/Envafo (qw)×6 | pCR | |
长程vs.短程 放疗序贯化 疗免疫 | PRIME-RT NCT04621370 | 2020 | 英国 | Ⅱ | 48 | cT3b+, N+, EMVI+ or low rectal tumors | Arm1: (SCRT+FOLFOX×6)/Durva Arm2: (LCRT+FOLFOX×4)/Durva | CR |
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