TY - JOUR
T1 - Combined treatment of non-small cell lung cancer using radiotherapy and immunotherapy
T2 - challenges and updates
AU - Shang, Shijie
AU - Liu, Jie
AU - Verma, Vivek
AU - Wu, Meng
AU - Welsh, James
AU - Yu, Jinming
AU - Chen, Dawei
N1 - Funding Information:
The study was supported by funds from The National Key Research and Development Projects of China (2018YFC1312201), Radiation Oncology Innovate Unit, Chinese Academy of Medical Sciences (2019RU071), Academic Promotion Program of Shandong First Medical University (2019ZL002), Foundation of National Natural Science Foundation of China (81972863, 81627901 and 82030082) and Science Foundation of Shandong (ZR2020 LZL016).
Publisher Copyright:
© 2021 The Authors. Cancer Communications published by John Wiley & Sons Australia, Ltd. on behalf of Sun Yat-sen University Cancer Center
PY - 2021/11
Y1 - 2021/11
N2 - The efficacy of immunotherapy for advanced non-small cell lung cancer (NSCLC) remains unsatisfactory, as the majority of patients either do not experience an objective response or acquire secondary resistance. As a result, several methods to enhance the systemic efficacy of immunotherapy have been investigated, including a large area of active research by combining immunotherapy with radiation therapy (RT). Given the rapidly burgeoning concept of combining immunotherapy and RT for increasing therapeutic benefit, we review the progress in this field thus far and explore further avenues for enhancing this combination. This review commences with a discussion of the only two existing randomized trials (and a pooled analysis) showing that the addition of RT to immunotherapy improves the abscopal response rate, progression-free survival, and overall survival in metastatic NSCLC patients. We then discussed factors and biomarkers that may be associated with a proportionally greater benefit to additional RT, such as low programmed cell death protein ligand 1 (PD-L1) status, tumor mutational burden (TMB), and patient's immune function. Next, the implementation of RT to overcome immunotherapy resistance is discussed, including a mechanistic discussion and methods with which these mechanisms could be exploited. Lastly, the emerging role of low-dose RT is discussed, which may help to overcome inhibitory signals in the tumor stroma that limit T-cell infiltration. Taken together, given the current state of this rapidly expanding realm, these futuristic strategies may be reflected upon to further enhance the efficacy of immunotherapy for a wider group of patients.
AB - The efficacy of immunotherapy for advanced non-small cell lung cancer (NSCLC) remains unsatisfactory, as the majority of patients either do not experience an objective response or acquire secondary resistance. As a result, several methods to enhance the systemic efficacy of immunotherapy have been investigated, including a large area of active research by combining immunotherapy with radiation therapy (RT). Given the rapidly burgeoning concept of combining immunotherapy and RT for increasing therapeutic benefit, we review the progress in this field thus far and explore further avenues for enhancing this combination. This review commences with a discussion of the only two existing randomized trials (and a pooled analysis) showing that the addition of RT to immunotherapy improves the abscopal response rate, progression-free survival, and overall survival in metastatic NSCLC patients. We then discussed factors and biomarkers that may be associated with a proportionally greater benefit to additional RT, such as low programmed cell death protein ligand 1 (PD-L1) status, tumor mutational burden (TMB), and patient's immune function. Next, the implementation of RT to overcome immunotherapy resistance is discussed, including a mechanistic discussion and methods with which these mechanisms could be exploited. Lastly, the emerging role of low-dose RT is discussed, which may help to overcome inhibitory signals in the tumor stroma that limit T-cell infiltration. Taken together, given the current state of this rapidly expanding realm, these futuristic strategies may be reflected upon to further enhance the efficacy of immunotherapy for a wider group of patients.
KW - immune checkpoint inhibitors
KW - immunotherapy
KW - immunotherapy combined with radiotherapy
KW - low-dose radiotherapy
KW - non-small cell lung cancer
KW - radiotherapy
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U2 - 10.1002/cac2.12226
DO - 10.1002/cac2.12226
M3 - Review article
C2 - 34658186
AN - SCOPUS:85117078506
SN - 1000-467X
VL - 41
SP - 1086
EP - 1099
JO - Cancer Communications
JF - Cancer Communications
IS - 11
ER -