PMID- 36439117
OWN - NLM
STAT- MEDLINE
DCOM- 20221129
LR  - 20230427
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 13
DP  - 2022
TI  - Toxicity profile of combined immune checkpoint inhibitors and thoracic 
      radiotherapy in esophageal cancer: A meta-analysis and systematic review.
PG  - 1039020
LID - 10.3389/fimmu.2022.1039020 [doi]
LID - 1039020
AB  - BACKGROUND: Therapies based on the combination of immune checkpoint inhibitors 
      (ICIs) and thoracic radiotherapy (TRT) are transforming the treatment landscape 
      of esophageal cancer. Nevertheless, the available data on adverse events (AEs) 
      mainly stemmed from several prospective clinical trials and retrospective 
      studies, in which, AE data are often handled and reported with less rigor than 
      the primary beneficial outcomes of the study. Thus, we conducted a systematic 
      review to investigate the toxicity spectrum of these novel regimens. METHOD: We 
      searched for all prospective clinical trials investigating the role of ICIs 
      combined with TRT published between January 2010 and August 2022. Study articles 
      and conference proceedings involving esophageal cancers and reporting the overall 
      incidence or details of treatment-related AEs (trAEs) were synthesized to 
      determine the toxicity profile of combination treatment. We compared trAEs 
      between cancer type, programmed cell death 1 (PD-1) and programmed cell death 
      ligand 1 (PD-L1) inhibitors, and between sequential and concurrent administration 
      of ICIs and TRT to identify potentially high-risk patients. RESULTS: We obtained 
      toxicity data from 14 clinical trials involving 863 patients. The pooled overall 
      incidence was 88.97% for any-grade trAEs and 18.48% for high-grade trAEs. The 
      three most frequent non-hematologic any-grade trAEs were reactive cutaneous 
      capillary endothelial proliferation (RCCEP, 63.80%), esophagitis (51.54%), and 
      fatigue (33.63%). Meanwhile, RCCEP (15.69%) was the most common non-hematologic 
      high-grade trAE, followed by nausea (4.91%) and anorexia (3.81%). The occurrence 
      rates of any-grade and high-grade pneumonitis were 10.82% and 0.66%, 
      respectively. In subgroup analysis, the toxicity profiles of PD-1 and PD-L1 
      inhibitors were mostly similar, except for any-grade pneumonitis (15.20% vs 
      4.88%, p=0.03) and high-grade leukopenia (6.25% vs 59.09%, p=0.00). In addition, 
      concurrent treatment seemed to have a higher incidence of any-grade trAEs (95.20% 
      vs 70.85%, p=0.03) compared with sequential treatment. ESCC seems to have higher 
      incidence of any-grade hypothyroidism (22.55% vs 8.96%, p=0.049) compared to EAC. 
      CONCLUSION: Our study is the first systematic review to provide a toxicity 
      profile of trAEs in esophageal cancer patients who received ICIs combined with 
      TRT. Most AEs of this combination treatment are tolerable, although the incidence 
      of any-grade trAEs was higher in the concurrent group. The difference in 
      any-grade pneumonitis between PD-1 and PD-L1 inhibitor groups needs further 
      validation in a large clinical trial.
CI  - Copyright (c) 2022 Xu, Liu, Lu and Liang.
FAU - Xu, Tongzhen
AU  - Xu T
AD  - Department of Radiotherapy Oncology, National Cancer Center/National Clinical 
      Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences 
      and Peking Union Medical College, Beijing, China.
FAU - Liu, Yunsong
AU  - Liu Y
AD  - Department of Radiotherapy Oncology, National Cancer Center/National Clinical 
      Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences 
      and Peking Union Medical College, Beijing, China.
FAU - Lu, Xiaotong
AU  - Lu X
AD  - Department of Radiotherapy Oncology, National Cancer Center/National Clinical 
      Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences 
      and Peking Union Medical College, Beijing, China.
FAU - Liang, Jun
AU  - Liang J
AD  - Department of Radiotherapy Oncology, National Cancer Center/National Clinical 
      Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy 
      of Medical Sciences and Peking Union Medical College, Shenzhen, China.
LA  - eng
PT  - Meta-Analysis
PT  - Research Support, Non-U.S. Gov't
PT  - Systematic Review
DEP - 20221110
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Immune Checkpoint Inhibitors)
RN  - 0 (Programmed Cell Death 1 Receptor)
SB  - IM
EIN - Front Immunol. 2023 Apr 11;14:1193710. PMID: 37101827
MH  - Humans
MH  - *Immune Checkpoint Inhibitors/adverse effects
MH  - Programmed Cell Death 1 Receptor
MH  - Prospective Studies
MH  - Retrospective Studies
MH  - *Esophageal Neoplasms/drug therapy
PMC - PMC9685562
OTO - NOTNLM
OT  - esophageal cancer
OT  - immune checkpoint inhibitors
OT  - safety
OT  - systemic analysis
OT  - thoracic radiotherapy
OT  - toxicity profile
COIS- The 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- 2022/11/29 06:00
MHDA- 2022/11/30 06:00
PMCR- 2022/01/01
CRDT- 2022/11/28 04:31
PHST- 2022/09/07 00:00 [received]
PHST- 2022/10/24 00:00 [accepted]
PHST- 2022/11/28 04:31 [entrez]
PHST- 2022/11/29 06:00 [pubmed]
PHST- 2022/11/30 06:00 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2022.1039020 [doi]
PST - epublish
SO  - Front Immunol. 2022 Nov 10;13:1039020. doi: 10.3389/fimmu.2022.1039020. 
      eCollection 2022.