ABSTRACT
In recent years, immunotherapy has become the hottest topic in the field of oncology. Both the Keynote189 study and the Keynote407 study have confirmed that progression-free survival is significantly prolonged in patients who have been benefited from immune checkpoint blockades in lung cancer. In an article published in The New England Journal of Medicine in 2012, a case report of radiation abscopal effects caused by immunization combined with conventional radiotherapy has attracted great attention in the field of oncology. The Pacific study, published in 2017, expanded the indications for immunotherapy from advanced to locally-advanced non-small cell lung cancer. The second analysis of Keynote001, published in the Lancet Oncology in the same year, suggested that radiation therapy may mediate the immune memory effects, whereas the mechanism and time window are still unclear. With the publication of PEMBRO-RT study and several pieces of work by our team in recent years, various details of radiotherapy combined with immunotherapy (iRT) have become more mature. In clinical practice, iRT is involved in the full treatment of lung cancer. However, iRT is not a hodgepodge or stew that needs further refinement and sorting. In this article, the principles, efficacy in clinical practice, and exploration of the details of iRT were discussed.
ABSTRACT
Objective To investigate and compare the clinical effects of radiochemotherapy alone or in combination with adoptive immunotherapy with cytokine-induced killer ( CIK) cells in patients with locally advanced non-small cell lung cancer (NSCLC).Methods The clinical data of 125 patients with locally advanced NSCLC who were admitted from 2011 to 2012 and did not undergo surgery were analyzed retrospectively, and among these patients, 102 received radiochemotherapy alone ( control group) , and 23 received radiochemotherapy combined with adoptive immunotherapy with CIK cells ( multimodality therapy group) .The two groups were matched at a ratio of 1:2 using propensity score matching, and the factors considered included tumor stage, radiochemotherapy regimen, and outcome after radiochemotherapy.Then 59 patients ( 22 from the multimodality therapy group and 37 from the control group) were enrolled, and survival and tumor control were compared between the two groups.The Kaplan-Meier method was used to calculate survival rates and the log-rank test was used for survival difference analysis and univariate prognostic analysis.Results The 1-, 2-, and 3-year overall survival ( OS) rates were 73%, 32%, and 16%, respectively, in the control group, and 91%, 59%, and 41%, respectively, in the multimodality therapy group ( P=0.030) .The 1-, 2-, and 3-year progression-free survival rates were 61%, 21%, and 17%, respectively, in the control group, and 45%, 10%, and 10%, respectively, in the multimodality therapy group ( P=0.538) .As for the patients with stage ⅢB NSCLC, those in the multimodality therapy group had a significantly higher 3-year OS rate than those in the control group (47%vs.11%, P=0.026). In the patients receiving sequential chemoradiotherapy, those in the multimodality therapy group had a significantly higher 3-year OS rate than those in the control group ( 46%vs.11%, P=0.003) .As for the patients with squamous cell carcinoma, those in the multimodality therapy group had a significantly higher 3-year distant metastasis-free survival rate than those in the control group ( 73%vs.22%, P=0.029) .The two groups showed similar incidence rates of adverse events, and compared with the control group, the multimodality therapy group had a lower incidence rate of radiation pneumonitis (9%vs.15%, P=0.889) and a higher incidence rate of radiation esophagitis (12%vs.7%, P=0.097).Conclusions Some patients with locally advanced NSCLC can benefit from radiochemotherapy combined with adoptive immunotherapy with CIK cells, but the intended population, timing, and dose safety still need further investigation.