PMID- 36686751
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230201
IS  - 2234-943X (Print)
IS  - 2234-943X (Electronic)
IS  - 2234-943X (Linking)
VI  - 12
DP  - 2022
TI  - Efficacy of intra-arterial chemotherapy with sequential anti-PD-1 antibody in 
      unresectable gastric cancer: A retrospective real-world study.
PG  - 1015962
LID - 10.3389/fonc.2022.1015962 [doi]
LID - 1015962
AB  - BACKGROUND: The prognosis of unresectable gastric cancer is poor, while the 
      efficacy of anti-PD antibodies has not been evaluated. METHODS: Patients with 
      unresectable gastric cancer who received intra-arterial chemotherapy (IAC) with 
      sequential anti-PD-1 antibody as induction therapy in Jinling Hospital were 
      retrospectively analyzed. The primary outcome is R0 resection rate. The secondary 
      outcomes include safety, conversion surgery rate, overall survival (OS) and 
      progression free survival (PFS) after postoperative IAC and anti-PD-1 treatments. 
      Meanwhile, Tumor immunity in the microenvironment (TIME) before and after IAC was 
      comprehensively dissected with multiplex immunofluorescence in order to detect 
      possible mechanisms favoring anti-PD-1 treatment response. RESULTS: Between May 
      2019 and October 2020, 36 patients received at least one cycle of IAC with 
      sequential anti-PD-1 antibody in our institution. The objective response was 
      achieved in 28 patients (77.8%). Thirty patients (83.3%) successfully underwent 
      conversion surgery, among which R0 resection was managed in 25/30 patients, and 
      23.3% (7/30) was assessed as pathological complete remission. During the median 
      follow-up period of 19.7 months, patients who underwent R0 resection displayed 
      superior OS (HR 0.14 [95% CI 0.04-0.50], P < 0.0001) and PFS (HR 0.11 
      [0.03-0.44], P < 0.0001) than those who did not. Grade 3 adverse events (AEs) 
      were only encountered in 19.4% patients, no grade 4 AEs observed. In TIME 
      analysis, the number of tertiary lymphoid structures (TLSs) (P = 0.004) were 
      greatly induced by IAC, as well as CD8(+) T cells (P = 0.011) and PD-1(+) cells 
      (P = 0.025). Meanwhile, Tumor associated macrophages shifted towards anti-tumor 
      M1-like subtypes, with CD68(+)CD163(+) M2-like subpopulation significantly 
      decreased (P = 0.04). CONCLUSION: Preoperative IAC with sequential anti-PD-1 
      antibody exhibited promising clinical benefit for unresectable gastric cancer 
      with remarkable conversion rate and R0 resection rate, and also prolonged 
      survival as postoperative regimen. TIME transformation induced by ICA might 
      mediate the additive effect with the immune checkpoint inhibitor.
CI  - Copyright (c) 2023 Xiang, Guo, Li, Ma, Zhu, Abdulla, Li, Zhang and Huang.
FAU - Xiang, Xiaosong
AU  - Xiang X
AD  - Department of General Surgery, Jinling Hospital, School of Medicine, Nanjing 
      University, Nanjing, China.
FAU - Guo, Feilong
AU  - Guo F
AD  - Department of General Surgery, Jinling Hospital, School of Medicine, Nanjing 
      University, Nanjing, China.
FAU - Li, Guoli
AU  - Li G
AD  - Department of General Surgery, Jinling Hospital, School of Medicine, Nanjing 
      University, Nanjing, China.
FAU - Ma, Long
AU  - Ma L
AD  - Department of General Surgery, Jinling Hospital, School of Medicine, Nanjing 
      University, Nanjing, China.
FAU - Zhu, Xi
AU  - Zhu X
AD  - Department of General Surgery, Jinling Hospital, School of Medicine, Nanjing 
      University, Nanjing, China.
FAU - Abdulla, Zulpikar
AU  - Abdulla Z
AD  - Department of General Surgery, Jinling Hospital, School of Medicine, Nanjing 
      University, Nanjing, China.
FAU - Li, Jiafei
AU  - Li J
AD  - Department of Biostatistics, Columbia University, New York, NY, United States.
FAU - Zhang, Junling
AU  - Zhang J
AD  - The Medical Department, 3D Medicines Inc., Shanghai, China.
FAU - Huang, Mengli
AU  - Huang M
AD  - The Medical Department, 3D Medicines Inc., Shanghai, China.
LA  - eng
PT  - Journal Article
DEP - 20230105
PL  - Switzerland
TA  - Front Oncol
JT  - Frontiers in oncology
JID - 101568867
PMC - PMC9849699
OTO - NOTNLM
OT  - anti-PD-1 antibody
OT  - conversion therapy
OT  - immune-based combination therapies
OT  - intra-arterial chemotherapy
OT  - unresectable gastric cancer
COIS- Authors JZ and MH were employed by 3D Medicines Inc. The remaining authors 
      declare that the research was conducted in the absence of any commercial or 
      financial relationships that could be construed as a potential conflict of 
      interest.
EDAT- 2023/01/24 06:00
MHDA- 2023/01/24 06:01
PMCR- 2022/01/01
CRDT- 2023/01/23 04:54
PHST- 2022/08/10 00:00 [received]
PHST- 2022/12/14 00:00 [accepted]
PHST- 2023/01/23 04:54 [entrez]
PHST- 2023/01/24 06:00 [pubmed]
PHST- 2023/01/24 06:01 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fonc.2022.1015962 [doi]
PST - epublish
SO  - Front Oncol. 2023 Jan 5;12:1015962. doi: 10.3389/fonc.2022.1015962. eCollection 
      2022.